# NM_031942.5(CDCA7):c.702A>G (p.Gln234=)

https://sugi.bio/variant/cdca7-p-gln234

## Summary

**CDCA7 p.Gln234= (c.702A>G)** is classified **Uncertain significance** in CDCA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-10). Very rare (popmax 0.000255%, nfe).

**At a glance:** Uncertain significance · review: Single submitter · rsID rs761247476 · 1 submitter · very rare (popmax 0.000255%, nfe)

## For patients & families {#patients}

This is a change in the CDCA7 gene that is currently of uncertain significance — a definitive interpretation has not yet been established, submitted by 1 submitter.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CDCA7](https://sugi.bio/atlas/gene/CDCA7/) |
| Protein change (HGVS p.) | p.Gln234= |
| Coding change (HGVS c.) | c.702A>G |
| MANE Select transcript | [NM_031942](https://www.ncbi.nlm.nih.gov/nuccore/NM_031942) |
| dbSNP | [rs761247476](https://www.ncbi.nlm.nih.gov/snp/rs761247476/) |
| Variant type | single nucleotide variant |
| Location | chr2:173364797-173364797 (GRCh38) |
| ClinVar | [VCV1960748](https://www.ncbi.nlm.nih.gov/clinvar/variation/1960748/) |

**All HGVS expressions:** `NC_000002.11:g.174229525A>G`, `NC_000002.12:g.173364797A>G`, `NG_047202.1:g.15781A>G`, `NM_031942.5:c.702A>G`, `NM_145810.3:c.465A>G`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation and, for splice-region changes, SpliceAI (below), not from a missing predictor score.
- SpliceAI predicts **acceptor gain** (Δ 0.78) — a splice-altering prediction on an uncertain variant — a signal for review
- Conservation: phyloP -0.029, GERP -5.19 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 14.35**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI deltas (raw): acceptor loss **0.05**, donor loss **0.00**, acceptor gain **0.78**, donor gain **0.00**. Largest is acceptor gain.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.78**, donor gain **0.00**.
- Pangolin: Δ**0.50** (gain), gain 0.50 / loss 0.09. Agrees with SpliceAI. An independent predictor to SpliceAI — a different model trained on different data. *Descriptive; ClinGen's SVI calibration covers SpliceAI, not Pangolin, so no ACMG code is assigned.*
- Population frequency (gnomAD v4.1): grpmax **0.000255%** (nfe) · FAF95 6.8e-05% · FAF99 1.9e-05% · 3/1,176,500 in the highest group · 4/1,602,032 alleles overall — very rare (popmax 0.000255%, nfe).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Remaining individuals (not grpmax-eligible) | 0.00161% | 62,012 |
| European (non-Finnish) (grpmax) | 0.000255% | 392,166 |

Remaining individuals shows a higher raw frequency than the grpmax group. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and "Remaining individuals" — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**CDCA7** population constraint: LOEUF 0.676, pLI 0.002565, missense-Z 1.8093. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **immunodeficiency-centromeric instability-facial anomalies syndrome 3** — Moderate (AR)

## Protein context {#protein}

Residue **234** lies in an α-helix.

AlphaFold model confidence (whole protein): pLDDT 68.93, 33% of residues very-high.

**2 experimental structure(s)** (PDB): [8TLK](https://www.rcsb.org/structure/8TLK), [8YV8](https://www.rcsb.org/structure/8YV8).

## What this gene does {#gene-function}

*Describes the biological roles of CDCA7 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** CDCA7's established molecular role includes hemi-methylated DNA-binding.


### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** hemi-methylated DNA-binding.

**Biological process:** regulation of cell population proliferation.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2022-08-10.

**Submitter consensus:** unanimous (1/1 Uncertain significance).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Uncertain significance | criteria provided, single submitter | clinical testing | 2022-08-10 |

**Reported phenotype names (ClinVar):** not provided, none provided, RECLASSIFIED - ADRA2C POLYMORPHISM, RECLASSIFIED - ADRB1 POLYMORPHISM.

## Similar variants {#similar}

Related CDCA7 variant pages (same residue, condition, or type): [CDCA7 c.384+2T>C](/variant/cdca7-c-384-plus-2t-c), [CDCA7 p.Ala157Val](/variant/cdca7-p-ala157val), [CDCA7 p.Ala391Gly](/variant/cdca7-p-ala391gly), [CDCA7 p.Arg134Leu](/variant/cdca7-p-arg134leu), [CDCA7 p.Arg134Trp](/variant/cdca7-p-arg134trp), [CDCA7 p.Arg171Cys](/variant/cdca7-p-arg171cys), [CDCA7 p.Arg171Leu](/variant/cdca7-p-arg171leu), [CDCA7 p.Arg239Gln](/variant/cdca7-p-arg239gln).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 1960748). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*