Is CFAP46 p.Ala2016Gly (c.6047C>G) pathogenic?

CFAP46 p.Ala2016Gly (c.6047C>G) is classified Uncertain significance in CFAP46 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely benign (0.0909); Rare (popmax 0.412%, afr).

How common is CFAP46 p.Ala2016Gly (c.6047C>G) in the general population?

CFAP46 p.Ala2016Gly (c.6047C>G) is rare (popmax 0.412%, afr) (gnomAD).

What do computational predictors say about CFAP46 p.Ala2016Gly (c.6047C>G)?

AlphaMissense predicts likely benign (score 0.0909) — an in-silico prediction, not a clinical call.

CFAP46 p.Ala2016Gly

c.6047C>G · VCV4227020

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0909 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.412%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0909	likely benign
REVEL	0.033	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 0.23	GERP -1.4
Regional constraint	o/e 0.94	unconstrained · MANE · 134 kb · p 0.00093 · regional, not allelic
Overall
CADD	5.099	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 0.412% African / African-American · 309/75,052 alleles

Filtering AF 0.374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.359%

Overall 0.0212% 342/1,613,188 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.412%	243
Remaining individualsnot grpmax-eligible	0.0384%	2,604
Admixed American	0.00833%	12,006
South Asian	0.00329%	30,361
European (non-Finnish)	8.48e-05%	1,179,938

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.Ala2016Gly
Coding: c.6047C>G
MANE Select: NM_001200049
Type: single nucleotide variant
Location: chr10:132847227 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)
Residue 2016: the 'disordered' region

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

Similar variants

CFAP46 p.Ala2016Glu 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-ala2016gly (accessed [today's date]).

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