Is CFAP65 p.Pro671Ser (c.2011C>T) pathogenic?

CFAP65 p.Pro671Ser (c.2011C>T) is classified Uncertain significance in CFAP65 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.1805); Ultra-rare (popmax 0.0392%, amr).

How common is CFAP65 p.Pro671Ser (c.2011C>T) in the general population?

CFAP65 p.Pro671Ser (c.2011C>T) is ultra-rare (popmax 0.0392%, amr) (gnomAD).

What do computational predictors say about CFAP65 p.Pro671Ser (c.2011C>T)?

AlphaMissense predicts likely benign (score 0.1805) — an in-silico prediction, not a clinical call.

CFAP65 p.Pro671Ser

c.2011C>T · rs766591037 · VCV2392232

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1805 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0392%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1805	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -9.14	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 6.7	GERP -0.43, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 13 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	20.2	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 0.0392% Admixed American · 23/58,704 alleles

Filtering AF 0.0267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0227%

Overall 0.00151% 24/1,587,194 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0392%	2,552
European (non-Finnish)	8.59e-05%	1,163,956

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.Pro671Ser
Coding: c.2011C>T
MANE Select: NM_194302
dbSNP: rs766591037
Type: single nucleotide variant
Location: chr2:219027850 (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-pro671ser (accessed [today's date]).

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