Is CFAP65 p.Val653Ile (c.1957G>A) pathogenic?

CFAP65 p.Val653Ile (c.1957G>A) is classified Benign/Likely benign in CFAP65 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-18). AlphaMissense: likely benign (0.0639); Low-frequency (popmax 1.02%, afr).

How common is CFAP65 p.Val653Ile (c.1957G>A) in the general population?

CFAP65 p.Val653Ile (c.1957G>A) is low-frequency (popmax 1.02%, afr) (gnomAD).

What do computational predictors say about CFAP65 p.Val653Ile (c.1957G>A)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

CFAP65 p.Val653Ile

c.1957G>A · rs73090878 · VCV783354

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.02%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -5.93	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 -1.5	GERP -3.7
Regional constraint	o/e 0.86	unconstrained · MANE · 13 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	0.134	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 1.02% African / African-American · 740/72,544 alleles

Filtering AF 0.959% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.935%

Overall 0.062% 950/1,533,282 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.02%	98
Admixed American	0.147%	679
Remaining individualsnot grpmax-eligible	0.119%	842
Ashkenazi Jewishnot grpmax-eligible	0.0538%	1,860
Middle Eastern	0.0531%	1,883
European (non-Finnish)	0.00456%	21,930

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: CFAP65
Protein: p.Val653Ile
Coding: c.1957G>A
MANE Select: NM_194302
dbSNP: rs73090878
Type: single nucleotide variant
Location: chr2:219027904 (GRCh38)
Gene constraint: LOEUF 0.85 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.03

Full CFAP65 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP65 p.Arg1231= Benign ★★ same type
CFAP65 p.Arg1545Gln Benign ★★ same type
CFAP65 p.Arg760Gln Benign ★★ same type
CFAP65 p.Asp1313= Likely benign ★★ same type
CFAP65 p.Leu1127= Benign/Likely benign ★★ same type
CFAP65 p.Leu1523= Benign/Likely benign ★★ same type
CFAP65 p.Leu1906= Benign/Likely benign ★★ same type
CFAP65 p.Lys1805= 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/cfap65-p-val653ile (accessed [today's date]).

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