# NM_001010940.3(CFAP95):c.366C>T (p.Ser122=)

https://sugi.bio/variant/cfap95-p-ser122

## Summary

**CFAP95 p.Ser122= (c.366C>T)** is classified **Benign** in CFAP95 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-12-28). Low-frequency (popmax 3.1%, afr).

**At a glance:** Benign · review: Multiple submitters · rsID rs7851894 · 2 submitters · low-frequency (popmax 3.1%, afr)

## For patients & families {#patients}

This is a change in the CFAP95 gene that is classified as benign — not considered disease-causing, submitted by 2 submitters.

*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 | [CFAP95](https://sugi.bio/atlas/gene/CFAP95/) |
| Protein change (HGVS p.) | p.Ser122= |
| Coding change (HGVS c.) | c.366C>T |
| MANE Select transcript | [NM_001010940](https://www.ncbi.nlm.nih.gov/nuccore/NM_001010940) |
| dbSNP | [rs7851894](https://www.ncbi.nlm.nih.gov/snp/rs7851894/) |
| Variant type | single nucleotide variant |
| Location | chr9:69856659-69856659 (GRCh38) |
| ClinVar | [VCV714426](https://www.ncbi.nlm.nih.gov/clinvar/variation/714426/) |

**All HGVS expressions:** `NC_000009.11:g.72471575C>T`, `NC_000009.12:g.69856659C>T`, `NM_001010940.3:c.366C>T`, `NM_001308084.2:c.366C>T`, `NM_001308085.2:c.69C>T`, `NM_001308086.2:c.69C>T`, `NR_131756.2:n.320C>T`, `NR_131757.2:n.320C>T`

## 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 (below), not from a missing predictor score.
- Conservation: phyloP 0.134, GERP -0.3, phastCons 0.491 — weakly conserved position
- CADD: **PHRED 10.93**. 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: **below the reporting threshold**. This position is scored for a different substitution (C>A, Δ0.33 donor loss), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency (gnomAD v4.1): grpmax **3.1%** (afr) · FAF95 3% · FAF99 2.95% · 2,317/74,730 in the highest group · 2,675/1,607,242 alleles overall — low-frequency (popmax 3.1%, afr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 3.1% | 32 |
| Remaining individuals (not grpmax-eligible) | 0.191% | 523 |
| Admixed American | 0.183% | 546 |
| Middle Eastern | 0.165% | 605 |
| South Asian | 0.0122% | 8,226 |
| European (non-Finnish) | 0.0091% | 10,984 |
| Finnish (not grpmax-eligible) | 0.00313% | 31,989 |

*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.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 63.03, 0% of residues very-high.

**2 experimental structure(s)** (PDB): [7UNG](https://www.rcsb.org/structure/7UNG), [8J07](https://www.rcsb.org/structure/8J07).

## Clinical significance {#significance}

**Benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2017-12-28.

**Submitter consensus:** unanimous (2/2 Benign).

**Submission history:** 2 submissions (2017); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2017-12-28 |
| Breakthrough Genomics, Breakthrough Genomics | Benign | criteria provided, single submitter | not provided |  |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related CFAP95 variant pages (same residue, condition, or type): [CFAP95 c.381-6T>C](/variant/cfap95-c-381-minus-6t-c), [CFAP95 p.Arg80Gln](/variant/cfap95-p-arg80gln), [CFAP95 p.His169Arg](/variant/cfap95-p-his169arg), [CFAP95 p.Tyr156Cys](/variant/cfap95-p-tyr156cys), [CFAP95 p.Ser157=](/variant/cfap95-p-ser157).

### 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 714426). 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.*