Is CFAP91 p.Gln370His (c.1110G>C) pathogenic?

CFAP91 p.Gln370His (c.1110G>C) is classified Uncertain significance in CFAP91 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: ambiguous (0.3781); Rare (popmax 0.985%, afr).

How common is CFAP91 p.Gln370His (c.1110G>C) in the general population?

CFAP91 p.Gln370His (c.1110G>C) is rare (popmax 0.985%, afr) (gnomAD).

What do computational predictors say about CFAP91 p.Gln370His (c.1110G>C)?

AlphaMissense predicts ambiguous (score 0.3781) — an in-silico prediction, not a clinical call.

CFAP91 p.Gln370His

c.1110G>C · VCV4652989

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3781 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.985%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3781	ambiguous
REVEL	0.143	moderately benign-leaning
SaProt	LLR -7.82	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.77	acceptor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.72	GERP -1.2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 48 kb · p 0.55 · regional, not allelic
Overall
CADD	20.5	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 0.985% African / African-American · 739/75,020 alleles

Filtering AF 0.926% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.903%

Overall 0.0537% 866/1,613,114 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.985%	102
Remaining individualsnot grpmax-eligible	0.096%	1,041
Admixed American	0.0868%	1,152
Middle Eastern	0.0495%	2,020
South Asian	0.0044%	22,740
European (non-Finnish)	0.000678%	147,415

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.Gln370His
Coding: c.1110G>C
MANE Select: NM_033364
Type: single nucleotide variant
Location: chr3:119732385 (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-gln370his (accessed [today's date]).

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