Is CLEC3B p.Val202Met (c.604G>A) pathogenic?

CLEC3B p.Val202Met (c.604G>A) is classified Uncertain significance in CLEC3B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: ambiguous (0.3596); Ultra-rare (popmax 0.0135%, eas).

How common is CLEC3B p.Val202Met (c.604G>A) in the general population?

CLEC3B p.Val202Met (c.604G>A) is ultra-rare (popmax 0.0135%, eas) (gnomAD).

What do computational predictors say about CLEC3B p.Val202Met (c.604G>A)?

AlphaMissense predicts ambiguous (score 0.3596) — an in-silico prediction, not a clinical call.

CLEC3B p.Val202Met

c.604G>A · rs770774345 · VCV2535524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3596 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, eas)

Computational evidence

Protein change
AlphaMissense	0.3596	ambiguous
REVEL	0.292	indeterminate
SaProt	LLR -5.93	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 9,558 bp · p 0.11 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0135% East Asian · 6/44,350 alleles

Filtering AF 0.00584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00398%

Overall 0.000378% 6/1,588,444 alleles · ultra-rare

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: CLEC3B
Protein: p.Val202Met
Coding: c.604G>A
MANE Select: NM_003278
dbSNP: rs770774345
Type: single nucleotide variant
Location: chr3:45035919 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.85 · 4 PDB

Full CLEC3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC3B p.Val202Leu Uncertain significance ★ ⚠ same residue
CLEC3B p.Ala153Ser Uncertain significance ★ ⚠ same type
CLEC3B p.Ala163Val Uncertain significance ★ ⚠ same type
CLEC3B p.Arg151Pro Uncertain significance ★ ⚠ same type
CLEC3B p.Asn114Lys Uncertain significance ★ ⚠ same type
CLEC3B p.Asp166Glu Uncertain significance ★ ⚠ same type
CLEC3B p.Asp191Tyr Uncertain significance ★ ⚠ same type
CLEC3B p.Asp97Gly 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/clec3b-p-val202met (accessed [today's date]).

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