Is CFAP97 p.Pro76Ser (c.226C>T) pathogenic?

CFAP97 p.Pro76Ser (c.226C>T) is classified Uncertain significance in CFAP97 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-19). AlphaMissense: likely benign (0.0715); Very rare (popmax 0.00333%, amr).

How common is CFAP97 p.Pro76Ser (c.226C>T) in the general population?

CFAP97 p.Pro76Ser (c.226C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CFAP97 p.Pro76Ser (c.226C>T)?

AlphaMissense predicts likely benign (score 0.0715) — an in-silico prediction, not a clinical call.

CFAP97 p.Pro76Ser

c.226C>T · VCV3266558

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0715 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0715	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -4.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.13	GERP -2.2
Regional constraint	o/e 1.06	unconstrained · MANE · 28 kb · p 0.14 · regional, not allelic
Overall
CADD	0.021	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 0.00333% Admixed American · 2/59,970 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000868% 14/1,613,600 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,985
Remaining individualsnot grpmax-eligible	0.0016%	62,456
South Asian	0.0011%	91,028
European (non-Finnish)	0.000848%	117,978

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: CFAP97
Protein: p.Pro76Ser
Coding: c.226C>T
MANE Select: NM_020827
Type: single nucleotide variant
Location: chr4:185190971 (GRCh38)
Gene constraint: LOEUF 1.095 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.55
Residue 76: the 'disordered' region

Full CFAP97 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP97 p.Glu383= Benign ★★ same type
CFAP97 p.Thr499Met Benign ★★ same type
CFAP97 p.Ala152Gly Uncertain significance ★ ⚠ same type
CFAP97 p.Ala448Thr Uncertain significance ★ ⚠ same type
CFAP97 p.Arg381Ser Uncertain significance ★ ⚠ same type
CFAP97 p.Arg389Gln Uncertain significance ★ ⚠ same type
CFAP97 p.Arg457His Uncertain significance ★ ⚠ same type
CFAP97 p.Arg479Trp Uncertain significance ★ ⚠ 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/cfap97-p-pro76ser (accessed [today's date]).

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