Is CFAP46 p.Arg2512Trp (c.7534C>T) pathogenic?

CFAP46 p.Arg2512Trp (c.7534C>T) is classified Uncertain significance in CFAP46 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-26). AlphaMissense: likely benign (0.132); Ultra-rare (popmax 0.0118%, amr).

How common is CFAP46 p.Arg2512Trp (c.7534C>T) in the general population?

CFAP46 p.Arg2512Trp (c.7534C>T) is ultra-rare (popmax 0.0118%, amr) (gnomAD).

What do computational predictors say about CFAP46 p.Arg2512Trp (c.7534C>T)?

AlphaMissense predicts likely benign (score 0.132) — an in-silico prediction, not a clinical call.

CFAP46 p.Arg2512Trp

c.7534C>T · VCV3491311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.132 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0118%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.132	likely benign
REVEL	0.065	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -2.3, phastCons 0.43
Regional constraint	o/e 0.94	unconstrained · MANE · 134 kb · p 0.00093 · regional, not allelic
Overall
CADD	18.78	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 0.0118% Admixed American · 7/59,358 alleles

Filtering AF 0.00549% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00469%

Overall 0.00579% 93/1,606,884 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0118%	8,480
Remaining individualsnot grpmax-eligible	0.00804%	12,442
European (non-Finnish)	0.00629%	15,906
South Asian	0.00557%	17,955
Finnishnot grpmax-eligible	0.0016%	62,666
African / African-American	0.00134%	74,818

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.Arg2512Trp
Coding: c.7534C>T
MANE Select: NM_001200049
Type: single nucleotide variant
Location: chr10:132810999 (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.Arg2512Gln Uncertain significance ★ ⚠ same residue
CFAP46 p.Arg2512Gly 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

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-arg2512trp (accessed [today's date]).

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