Is CFAP69 p.Ile17Val (c.49A>G) pathogenic?

CFAP69 p.Ile17Val (c.49A>G) is classified Uncertain significance in CFAP69 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-08-31). AlphaMissense: likely benign (0.0671); Rare (popmax 0.516%, eas).

How common is CFAP69 p.Ile17Val (c.49A>G) in the general population?

CFAP69 p.Ile17Val (c.49A>G) is rare (popmax 0.516%, eas) (gnomAD).

What do computational predictors say about CFAP69 p.Ile17Val (c.49A>G)?

AlphaMissense predicts likely benign (score 0.0671) — an in-silico prediction, not a clinical call.

CFAP69 p.Ile17Val

c.49A>G · VCV3357350

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0671 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.516%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0671	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -5.54	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 -0.63	GERP -6.3
Regional constraint	o/e 0.97	unconstrained · MANE · 65 kb · p 0.37 · regional, not allelic
Overall
CADD	0.009	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 0.516% East Asian · 199/38,570 alleles

Filtering AF 0.457% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.435%

Overall 0.0239% 372/1,553,586 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.516%	194
Remaining individualsnot grpmax-eligible	0.142%	703
Admixed American	0.0403%	2,484
African / African-American	0.0385%	2,600
South Asian	0.0318%	3,140
European (non-Finnish)	0.00121%	82,406

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.Ile17Val
Coding: c.49A>G
MANE Select: NM_001039706
Type: single nucleotide variant
Location: chr7:90245473 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48
Residue 17: the 'disordered' region

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-ile17val (accessed [today's date]).

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