Is CFAP91 p.Ala249Asp (c.746C>A) pathogenic?

CFAP91 p.Ala249Asp (c.746C>A) is classified Uncertain significance in CFAP91 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.3016); Very rare (popmax 0.000678%, nfe).

How common is CFAP91 p.Ala249Asp (c.746C>A) in the general population?

CFAP91 p.Ala249Asp (c.746C>A) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about CFAP91 p.Ala249Asp (c.746C>A)?

AlphaMissense predicts likely benign (score 0.3016) — an in-silico prediction, not a clinical call.

CFAP91 p.Ala249Asp

c.746C>A · rs2053781227 · VCV3143726

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3016 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3016	likely benign
REVEL	0.297	indeterminate
SaProt	LLR -11.09	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -0.12, phastCons 0.98
Regional constraint	o/e 1.02	unconstrained · MANE · 48 kb · p 0.55 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,854 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000547% 8/1,461,494 alleles · very rare

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: CFAP91
Protein: p.Ala249Asp
Coding: c.746C>A
MANE Select: NM_033364
dbSNP: rs2053781227
Type: single nucleotide variant
Location: chr3:119726234 (GRCh38)
Gene constraint: LOEUF 1.129 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.20 · 1 PDB

Full CFAP91 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP91 c.359+1G>A Likely pathogenic ★ same type
CFAP91 p.Gln545Ter Likely pathogenic ★ same type
CFAP91 c.501-3T>C Uncertain significance ★ same type
CFAP91 p.Ala256Thr Uncertain significance ★ ⚠ same type
CFAP91 p.Ala449Val Uncertain significance ★ ⚠ same type
CFAP91 p.Ala598Ser Uncertain significance ★ ⚠ same type
CFAP91 p.Ala718Thr Uncertain significance ★ ⚠ same type
CFAP91 p.Arg102Trp 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/cfap91-p-ala249asp (accessed [today's date]).

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