Is CLEC4A p.Val92Ala (c.275T>C) pathogenic?

CLEC4A p.Val92Ala (c.275T>C) is classified Uncertain significance in CLEC4A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-01). AlphaMissense: likely benign (0.1336); Very rare (popmax 0.00338%, amr).

How common is CLEC4A p.Val92Ala (c.275T>C) in the general population?

CLEC4A p.Val92Ala (c.275T>C) is very rare (popmax 0.00338%, amr) (gnomAD).

What do computational predictors say about CLEC4A p.Val92Ala (c.275T>C)?

AlphaMissense predicts likely benign (score 0.1336) — an in-silico prediction, not a clinical call.

CLEC4A p.Val92Ala

c.275T>C · rs902482811 · VCV2286864

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1336 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00338%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1336	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.1	GERP -2.8
Regional constraint	o/e 0.92	unconstrained · MANE · 14 kb · p 0.19 · regional, not allelic
Overall
CADD	8.809	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 0.00338% Admixed American · 2/59,112 alleles

Filtering AF 0.000561% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00021%

Overall 0.000249% 4/1,608,954 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00338%	29,556
European (non-Finnish)	0.00017%	588,828

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: CLEC4A
Protein: p.Val92Ala
Coding: c.275T>C
MANE Select: NM_016184
dbSNP: rs902482811
Type: single nucleotide variant
Location: chr12:8129339 (GRCh38)
Gene constraint: LOEUF 1.086 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.95 · 2 PDB

Full CLEC4A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC4A p.Arg194Cys Uncertain significance ★★ ⚠ same type
CLEC4A p.Ter238Arg Benign ★★ same type
CLEC4A p.Ala102Pro Uncertain significance ★ ⚠ same type
CLEC4A p.Arg174Gln Uncertain significance ★ ⚠ same type
CLEC4A p.Arg202Cys Uncertain significance ★ ⚠ same type
CLEC4A p.Arg202His Uncertain significance ★ ⚠ same type
CLEC4A p.Arg209Cys Uncertain significance ★ ⚠ same type
CLEC4A p.Arg209His 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/clec4a-p-val92ala (accessed [today's date]).

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