Is CFAP57 p.Ser91Cys (c.272C>G) pathogenic?

CFAP57 p.Ser91Cys (c.272C>G) is classified Uncertain significance in CFAP57 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely benign (0.117); Ultra-rare (popmax 0.0312%, eas).

How common is CFAP57 p.Ser91Cys (c.272C>G) in the general population?

CFAP57 p.Ser91Cys (c.272C>G) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about CFAP57 p.Ser91Cys (c.272C>G)?

AlphaMissense predicts likely benign (score 0.117) — an in-silico prediction, not a clinical call.

CFAP57 p.Ser91Cys

c.272C>G · rs117288508 · VCV2553340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.117 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.117	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -8.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.5	GERP -0.51, phastCons 0.61
Regional constraint	o/e 0.90	unconstrained · MANE · 81 kb · p 0.00012 · regional, not allelic
Overall
CADD	21.2	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 0.0312% East Asian · 14/44,896 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.000991% 16/1,614,238 alleles · ultra-rare exomes 10/1,461,890 · genomes 6/152,348 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,207
Remaining individualsnot grpmax-eligible	0.0032%	31,254

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: CFAP57
Protein: p.Ser91Cys
Coding: c.272C>G
MANE Select: NM_001378189
dbSNP: rs117288508
Type: single nucleotide variant
Location: chr1:43181648 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 1 PDB

Full CFAP57 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP57 p.Gln125Arg Likely benign ★★ ⚠ same type
CFAP57 p.Ile322Met Likely benign ★★ same type
CFAP57 p.Ser614= Likely benign ★★ same type
CFAP57 p.Arg411Ter Likely pathogenic ★ same type
CFAP57 p.Arg958Ter Pathogenic ★ same type
CFAP57 c.1929+122A>C Uncertain significance ★ same type
CFAP57 c.1929+139C>A Uncertain significance ★ same type
CFAP57 c.1929+154A>T 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/cfap57-p-ser91cys (accessed [today's date]).

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