Is CFAP46 p.Ala2595Val (c.7784C>T) pathogenic?

CFAP46 p.Ala2595Val (c.7784C>T) is classified Uncertain significance in CFAP46 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-20). AlphaMissense: likely benign (0.149); Very rare (popmax 0.0052%, amr).

How common is CFAP46 p.Ala2595Val (c.7784C>T) in the general population?

CFAP46 p.Ala2595Val (c.7784C>T) is very rare (popmax 0.0052%, amr) (gnomAD).

What do computational predictors say about CFAP46 p.Ala2595Val (c.7784C>T)?

AlphaMissense predicts likely benign (score 0.149) — an in-silico prediction, not a clinical call.

CFAP46 p.Ala2595Val

c.7784C>T · rs1412140287 · VCV3143523

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.149 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0052%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.149	likely benign
REVEL	0.012	strongly benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.64	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.13	GERP -1.6, phastCons 0.001
Regional constraint	o/e 0.94	unconstrained · MANE · 134 kb · p 0.00093 · regional, not allelic
Overall
CADD	15.86	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 0.0052% Admixed American · 3/57,670 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000683%

Overall 0.000313% 5/1,599,740 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0052%	19,223
South Asian	0.00224%	44,559

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: CFAP46
Protein: p.Ala2595Val
Coding: c.7784C>T
MANE Select: NM_001200049
dbSNP: rs1412140287
Type: single nucleotide variant
Location: chr10:132808785 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)

Full CFAP46 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP46 p.Ala2595Thr Uncertain significance ★ ⚠ same residue
CFAP46 p.Ala1708Val Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1742Glu Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1742Val Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1746Glu Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1788Val Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1806Val Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1811Val Uncertain significance ★ ⚠ 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/cfap46-p-ala2595val (accessed [today's date]).

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