Is CFAP65 p.Thr292Met (c.875C>T) pathogenic?

CFAP65 p.Thr292Met (c.875C>T) is classified Likely benign in CFAP65 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.084); Ultra-rare (popmax 0.066%, mid).

How common is CFAP65 p.Thr292Met (c.875C>T) in the general population?

CFAP65 p.Thr292Met (c.875C>T) is ultra-rare (popmax 0.066%, mid) (gnomAD).

What do computational predictors say about CFAP65 p.Thr292Met (c.875C>T)?

AlphaMissense predicts likely benign (score 0.084) — an in-silico prediction, not a clinical call.

CFAP65 p.Thr292Met

c.875C>T · rs137890879 · VCV3143619

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.084 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.084	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -8.10	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 1.2	GERP -3.2, phastCons 0.001
Regional constraint	o/e 0.86	unconstrained · MANE · 13 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	5.815	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 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0399% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0387%

Overall 0.0348% 561/1,613,828 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,516
European (non-Finnish)	0.0431%	2,323
Remaining individualsnot grpmax-eligible	0.032%	3,124
Admixed American	0.0317%	3,157
South Asian	0.0055%	18,198
East Asian	0.00446%	22,440
African / African-American	0.00267%	37,521
Finnishnot grpmax-eligible	0.00156%	63,996

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.Thr292Met
Coding: c.875C>T
MANE Select: NM_194302
dbSNP: rs137890879
Type: single nucleotide variant
Location: chr2:219031246 (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-thr292met (accessed [today's date]).

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