Is CFAP276 p.Arg46Gln (c.137G>A) pathogenic?

CFAP276 p.Arg46Gln (c.137G>A) is classified Uncertain significance in CFAP276 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely benign (0.148); Ultra-rare (popmax 0.0183%, amr).

How common is CFAP276 p.Arg46Gln (c.137G>A) in the general population?

CFAP276 p.Arg46Gln (c.137G>A) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about CFAP276 p.Arg46Gln (c.137G>A)?

AlphaMissense predicts likely benign (score 0.148) — an in-silico prediction, not a clinical call.

CFAP276 p.Arg46Gln

c.137G>A · rs200958119 · VCV3143440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.148 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.148	likely benign
REVEL	0.34	indeterminate
SaProt	LLR -7.06	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 0.51, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 6,648 bp · p 0.25 · regional, not allelic
Overall
CADD	24.9	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 0.0183% Admixed American · 11/59,998 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.0136% 219/1,613,778 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,454
European (non-Finnish)	0.0163%	6,145
Remaining individualsnot grpmax-eligible	0.016%	6,248
Finnishnot grpmax-eligible	0.00625%	15,994
African / African-American	0.00267%	37,494

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: CFAP276
Protein: p.Arg46Gln
Coding: c.137G>A
MANE Select: NM_001245025
dbSNP: rs200958119
Type: single nucleotide variant
Location: chr1:109107982 (GRCh38)
Structure: AlphaFold pLDDT 67.55 · 2 PDB

Full CFAP276 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP276 p.Arg10Ser Uncertain significance ★ same type
CFAP276 p.Arg160Ter Uncertain significance ★ same type
CFAP276 p.Gln143Glu Uncertain significance ★ ⚠ same type
CFAP276 c.45+725G>T Likely benign ★ same type
CFAP276 p.Ile122Asn Uncertain significance ⚠ same type
CFAP276 p.Lys28Ile 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/cfap276-p-arg46gln (accessed [today's date]).

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