Is CFAP69 p.Gln76His (c.228G>C) pathogenic?

CFAP69 p.Gln76His (c.228G>C) is classified Uncertain significance in CFAP69 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely benign (0.1152); Ultra-rare (popmax 0.0175%, mid).

How common is CFAP69 p.Gln76His (c.228G>C) in the general population?

CFAP69 p.Gln76His (c.228G>C) is ultra-rare (popmax 0.0175%, mid) (gnomAD).

What do computational predictors say about CFAP69 p.Gln76His (c.228G>C)?

AlphaMissense predicts likely benign (score 0.1152) — an in-silico prediction, not a clinical call.

CFAP69 p.Gln76His

c.228G>C · rs754673874 · VCV2336523

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1152 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0175%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1152	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -7.42	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 -0.26	GERP 0.97, phastCons 0.018
Regional constraint	o/e 0.97	unconstrained · MANE · 65 kb · p 0.37 · regional, not allelic
Overall
CADD	21.0	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 0.0175% Middle Eastern · 1/5,716 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000412% 6/1,456,908 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0175%	5,716
Remaining individualsnot grpmax-eligible	0.00161%	62,284
European (non-Finnish)	0.00034%	294,274

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: CFAP69
Protein: p.Gln76His
Coding: c.228G>C
MANE Select: NM_001039706
dbSNP: rs754673874
Type: single nucleotide variant
Location: chr7:90258145 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48

Full CFAP69 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP69 p.Gln76Arg Uncertain significance ★ ⚠ same residue
CFAP69 p.Phe731Leu Uncertain significance ★★ ⚠ same type
CFAP69 p.Tyr819His Uncertain significance ★★ ⚠ same type
CFAP69 c.1857+47T>A Benign ★★ same type
CFAP69 c.682+50A>C Benign ★★ same type
CFAP69 p.Ala12= Benign ★★ same type
CFAP69 p.Ala182= Benign ★★ same type
CFAP69 p.Ala8= Benign/Likely benign ★★ 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/cfap69-p-gln76his (accessed [today's date]).

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