Is CFAP46 p.Met1884Val (c.5650A>G) pathogenic?

CFAP46 p.Met1884Val (c.5650A>G) is classified Uncertain significance in CFAP46 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-04). AlphaMissense: likely benign (0.1019); Ultra-rare (popmax 0.0164%, mid).

How common is CFAP46 p.Met1884Val (c.5650A>G) in the general population?

CFAP46 p.Met1884Val (c.5650A>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CFAP46 p.Met1884Val (c.5650A>G)?

AlphaMissense predicts likely benign (score 0.1019) — an in-silico prediction, not a clinical call.

CFAP46 p.Met1884Val

c.5650A>G · VCV4001525

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1019 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1019	likely benign
REVEL	0.026	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 -1.3	GERP -4.2
Regional constraint	o/e 0.94	unconstrained · MANE · 134 kb · p 0.00093 · regional, not allelic
Overall
CADD	1.662	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00124% 20/1,613,992 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
East Asian	0.00223%	44,886
South Asian	0.0022%	45,546
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.00119%	84,289

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.Met1884Val
Coding: c.5650A>G
MANE Select: NM_001200049
Type: single nucleotide variant
Location: chr10:132851230 (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.Ala1708Val Uncertain significance ★ ⚠ same type
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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
CFAP46 p.Ala1871Val 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-met1884val (accessed [today's date]).

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