Is CFAP69 p.Gln650Arg (c.1949A>G) pathogenic?

CFAP69 p.Gln650Arg (c.1949A>G) is classified Likely benign in CFAP69 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-05). AlphaMissense: likely benign (0.0475); Ultra-rare (popmax 0.0179%, eas).

How common is CFAP69 p.Gln650Arg (c.1949A>G) in the general population?

CFAP69 p.Gln650Arg (c.1949A>G) is ultra-rare (popmax 0.0179%, eas) (gnomAD).

What do computational predictors say about CFAP69 p.Gln650Arg (c.1949A>G)?

AlphaMissense predicts likely benign (score 0.0475) — an in-silico prediction, not a clinical call.

CFAP69 p.Gln650Arg

c.1949A>G · rs778864304 · VCV3143628

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0475 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0475	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -3.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.48 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.4	GERP 4.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 65 kb · p 0.37 · regional, not allelic
Overall
CADD	18.06	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 0.0179% East Asian · 8/44,714 alleles

Filtering AF 0.00886% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00643%

Overall 0.000558% 9/1,612,362 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0179%	5,589
Remaining individualsnot grpmax-eligible	0.0016%	62,394

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.Gln650Arg
Coding: c.1949A>G
MANE Select: NM_001039706
dbSNP: rs778864304
Type: single nucleotide variant
Location: chr7:90299958 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48
Residue 650: 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-gln650arg (accessed [today's date]).

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