Is CFAP96 p.Ser254Cys (c.761C>G) pathogenic?

CFAP96 p.Ser254Cys (c.761C>G) is classified Uncertain significance in CFAP96 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). AlphaMissense: likely benign (0.2482); Ultra-rare (popmax 0.053%, amr).

How common is CFAP96 p.Ser254Cys (c.761C>G) in the general population?

CFAP96 p.Ser254Cys (c.761C>G) is ultra-rare (popmax 0.053%, amr) (gnomAD).

What do computational predictors say about CFAP96 p.Ser254Cys (c.761C>G)?

AlphaMissense predicts likely benign (score 0.2482) — an in-silico prediction, not a clinical call.

CFAP96 p.Ser254Cys

c.761C>G · rs762381726 · VCV2406127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2482 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.053%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2482	likely benign
REVEL	0.45	indeterminate
SaProt	LLR -7.75	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.15 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.053% Admixed American · 27/50,980 alleles

Filtering AF 0.0374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0321%

Overall 0.00406% 63/1,551,456 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.053%	1,888
Middle Eastern	0.0166%	6,012
Remaining individualsnot grpmax-eligible	0.00832%	12,018
Finnishnot grpmax-eligible	0.00334%	29,944
African / African-American	0.00274%	36,514
European (non-Finnish)	0.00227%	44,113

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CFAP96
Protein: p.Ser254Cys
Coding: c.761C>G
MANE Select: NM_001114357
dbSNP: rs762381726
Type: single nucleotide variant
Location: chr4:185445010 (GRCh38)
Structure: AlphaFold pLDDT 74.34

Full CFAP96 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UFSP2 p.Ile13Thr Uncertain significance ★★ ⚠ same type
UFSP2 p.Leu85Val Uncertain significance ★★ ⚠ same type
UFSP2 c.333+11T>C Benign ★★ same type
UFSP2 c.-33C>T Benign ★★ same type
UFSP2 p.Asn235Ser Benign/Likely benign ★★ same type
UFSP2 p.Glu93= Benign/Likely benign ★★ same type
UFSP2 p.Ser79= Benign ★★ same type
UFSP2 p.Thr76= Benign/Likely benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cfap96-p-ser254cys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown