Is CFAP91 p.Arg292Leu (c.875G>T) pathogenic?

CFAP91 p.Arg292Leu (c.875G>T) is classified Uncertain significance in CFAP91 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.6363); Rare (popmax 0.149%, mid).

How common is CFAP91 p.Arg292Leu (c.875G>T) in the general population?

CFAP91 p.Arg292Leu (c.875G>T) is rare (popmax 0.149%, mid) (gnomAD).

What do computational predictors say about CFAP91 p.Arg292Leu (c.875G>T)?

AlphaMissense predicts likely pathogenic (score 0.6363) — an in-silico prediction, not a clinical call.

CFAP91 p.Arg292Leu

c.875G>T · rs201238294 · VCV2510696

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6363 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.149%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6363	likely pathogenic
REVEL	0.386	indeterminate
SaProt	LLR -14.47	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 48 kb · p 0.55 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.149% Middle Eastern · 9/6,060 alleles

Filtering AF 0.0874% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0811%

Overall 0.0172% 277/1,613,600 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.149%	673
South Asian	0.104%	957
Remaining individualsnot grpmax-eligible	0.0384%	2,604
European (non-Finnish)	0.012%	8,368
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,865
Admixed American	0.00667%	14,984
East Asian	0.00223%	44,848

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.Arg292Leu
Coding: c.875G>T
MANE Select: NM_033364
dbSNP: rs201238294
Type: single nucleotide variant
Location: chr3:119730234 (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.Ala249Asp 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

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-arg292leu (accessed [today's date]).

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