Is CFAP69 p.Val490Met (c.1468G>A) pathogenic?

CFAP69 p.Val490Met (c.1468G>A) is classified Benign in CFAP69 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-07-14). AlphaMissense: likely benign (0.0577); Common (popmax 99.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with spermatogenic failure 24.

What condition is associated with CFAP69 p.Val490Met (c.1468G>A)?

CFAP69 p.Val490Met (c.1468G>A) is associated with spermatogenic failure 24 (ClinVar).

What do computational predictors say about CFAP69 p.Val490Met (c.1468G>A)?

AlphaMissense predicts likely benign (score 0.0577) — an in-silico prediction, not a clinical call.

CFAP69 p.Val490Met

Q: How common is CFAP69 p.Val490Met (c.1468G>A) in the general population?

CFAP69 p.Val490Met (c.1468G>A) is common (popmax 99.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1468G>A · rs1029365 · VCV1192635

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0577 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 99.9%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spermatogenic failure 24

Computational evidence

Protein change
AlphaMissense	0.0577	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -7.12	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 3.5	GERP 3.3, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 65 kb · p 0.37 · regional, not allelic
Overall
CADD	15.72	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 99.9% East Asian · 43,387/43,450 alleles

Filtering AF 99.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.7%

Overall 79.1% 1,259,977/1,593,122 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	99.9%	1
Finnishnot grpmax-eligible	86.4%	1
South Asian	85.8%	1
African / African-American	85.5%	1
Admixed American	85.4%	1
Amishnot grpmax-eligible	80.3%	1
Remaining individualsnot grpmax-eligible	80%	1
Middle Eastern	79.7%	1
Ashkenazi Jewishnot grpmax-eligible	78.2%	1
European (non-Finnish)	76.7%	1

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.Val490Met
Coding: c.1468G>A
MANE Select: NM_001039706
dbSNP: rs1029365
Type: single nucleotide variant
Location: chr7:90282987 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48
Residue 490: a UniProt-annotated variant site (in spgf24); a UniProt-annotated variant site (in)

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

Disease context

spermatogenic failure 24 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP69 c.1857+47T>A Benign ★★ same condition
CFAP69 c.682+50A>C Benign ★★ same condition
CFAP69 p.Ser854Arg Benign ★★ same condition
CFAP69 p.Thr885Met Benign ★★ ⚠ same condition
CFAP69 c.860+1G>A Pathogenic same condition
CFAP69 p.Gln255Ter Pathogenic same condition
CFAP69 p.Trp216Ter Pathogenic same condition
CFAP69 p.Leu357fs Pathogenic same condition

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-val490met (accessed [today's date]).

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