Is CFAP69 p.Tyr482Cys (c.1445A>G) pathogenic?

CFAP69 p.Tyr482Cys (c.1445A>G) is classified Uncertain significance in CFAP69 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely benign (0.2383); Very rare (popmax 0.00456%, eas).

How common is CFAP69 p.Tyr482Cys (c.1445A>G) in the general population?

CFAP69 p.Tyr482Cys (c.1445A>G) is very rare (popmax 0.00456%, eas) (gnomAD).

What do computational predictors say about CFAP69 p.Tyr482Cys (c.1445A>G)?

AlphaMissense predicts likely benign (score 0.2383) — an in-silico prediction, not a clinical call.

CFAP69 p.Tyr482Cys

c.1445A>G · VCV4227135

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2383 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00456%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2383	likely benign
REVEL	0.346	indeterminate
SaProt	LLR -7.10	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 5.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 65 kb · p 0.37 · regional, not allelic
Overall
CADD	26.5	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 0.00456% East Asian · 2/43,860 alleles

Filtering AF 0.000756% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000283%

Overall 0.000207% 3/1,447,960 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00456%	21,930
South Asian	0.00113%	88,742

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.Tyr482Cys
Coding: c.1445A>G
MANE Select: NM_001039706
Type: single nucleotide variant
Location: chr7:90282964 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48
Residue 482: a UniProt-annotated variant site (in spgf24)

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

Similar variants

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
CFAP69 p.Arg106His 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-tyr482cys (accessed [today's date]).

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