# NM_016356.5(DCDC2):c.45C>A (p.Val15=)

https://sugi.bio/variant/dcdc2-p-val15

## Summary

**DCDC2 p.Val15= (c.45C>A)** is classified **Likely benign** in DCDC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-22). AlphaMissense: likely benign (0.198); Very rare (popmax 0.00288%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 66.

**At a glance:** Likely benign · review: Multiple submitters · rsID rs148029760 · 2 submitters · 2 linked conditions · AlphaMissense likely benign · very rare (popmax 0.00288%, nfe)

> **Built without this gene's context.** ClinVar files this variant under an overlapping gene, so its own gene's record set does not contain it and this page is assembled from the variant alone. Gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up — absent from this page, not from the data.

## For patients & families {#patients}

This is a change in the DCDC2 gene that is classified as likely benign — not considered disease-causing, submitted by 2 submitters, and is linked to autosomal recessive nonsyndromic hearing loss 66.

*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:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0022621/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [DCDC2](https://sugi.bio/atlas/gene/DCDC2/) |
| Protein change (HGVS p.) | p.Val15= |
| Coding change (HGVS c.) | c.45C>A |
| MANE Select transcript | [NM_016356](https://www.ncbi.nlm.nih.gov/nuccore/NM_016356) |
| dbSNP | [rs148029760](https://www.ncbi.nlm.nih.gov/snp/rs148029760/) |
| Variant type | single nucleotide variant |
| Location | chr6:24357706-24357706 (GRCh38) |
| ClinVar | [VCV1205790](https://www.ncbi.nlm.nih.gov/clinvar/variation/1205790/) |

**All HGVS expressions:** `NC_000006.11:g.24357934G>T`, `NC_000006.12:g.24357706G>T`, `NG_012829.2:g.30587C>A`, `NM_001195610.2:c.45C>A`, `NM_016356.5:c.45C>A`

## Computational & population evidence {#evidence}

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

- AlphaMissense **likely benign** (0.198)
- REVEL 0.574 (indeterminate)
- SaProt LLR -9.075 (tolerated) — agrees with AlphaMissense
- → **In-silico consensus:** AlphaMissense and SaProt both call this tolerated; REVEL makes no call
- Conservation: phyloP -0.449, GERP -3.41, phastCons 0.017 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 11.81**. 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: **not looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- Population frequency (gnomAD v4.1): grpmax **0.00288%** (nfe) · FAF95 0.00208% · FAF99 0.00183% · 34/1,179,540 in the highest group · 35/1,612,658 alleles overall — very rare (popmax 0.00288%, nfe).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| European (non-Finnish) (grpmax) | 0.00288% | 34,692 |
| Remaining individuals (not grpmax-eligible) | 0.0016% | 62,450 |

*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.*

## Clinical significance {#significance}

**Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2024-10-22.

**Submitter consensus:** unanimous (2/2 Likely benign).

**Submission history:** 2 submissions (2020–2024); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| GeneDx | Likely benign | criteria provided, single submitter | clinical testing | 2020-06-12 |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2024-10-22 |

## Associated conditions {#conditions}

[autosomal recessive nonsyndromic hearing loss 66](https://sugi.bio/atlas/disease/autosomal-recessive-nonsyndromic-hearing-loss-66/), [isolated neonatal sclerosing cholangitis](https://sugi.bio/atlas/disease/isolated-neonatal-sclerosing-cholangitis/).

**Reported phenotype names (ClinVar):** Autosomal recessive nonsyndromic hearing loss 66, not provided, Isolated neonatal sclerosing cholangitis, Deafness, autosomal recessive 66, Sclerosing cholangitis, neonatal, none provided.

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); 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 2026-10-14); 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 1205790). 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.*