Is CLEC2B p.Phe115Ile (c.343T>A) pathogenic?

CLEC2B p.Phe115Ile (c.343T>A) is classified Uncertain significance in CLEC2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: ambiguous (0.4551); Very rare (popmax 0.000137%).

How common is CLEC2B p.Phe115Ile (c.343T>A) in the general population?

CLEC2B p.Phe115Ile (c.343T>A) is very rare (popmax 0.000137%) (gnomAD).

What do computational predictors say about CLEC2B p.Phe115Ile (c.343T>A)?

AlphaMissense predicts ambiguous (score 0.4551) — an in-silico prediction, not a clinical call.

CLEC2B p.Phe115Ile

c.343T>A · VCV4003548

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4551 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000137%)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4551	ambiguous
REVEL	0.028	moderately benign-leaning
SaProt	LLR -12.05	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.2	GERP -3.8
Regional constraint	o/e 0.91	unconstrained · MANE · 9,268 bp · p 0.23 · regional, not allelic
Overall
CADD	0.996	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 0.000137%

Overall 0.000137% 2/1,459,792 alleles · very 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: CLEC2B
Protein: p.Phe115Ile
Coding: c.343T>A
MANE Select: NM_005127
Type: single nucleotide variant
Location: chr12:9853407 (GRCh38)
Gene constraint: LOEUF 1.404 · pLI 0.52 (gnomAD)
Structure: AlphaFold pLDDT 92.25
Residue 115: the c-type lectin domain; a disulfide bond

Full CLEC2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC2B p.Arg145Lys Uncertain significance ★ ⚠ same type
CLEC2B p.Arg147Gly Uncertain significance ★ ⚠ same type
CLEC2B p.Arg84Trp Uncertain significance ★ ⚠ same type
CLEC2B p.Asn100Lys Uncertain significance ★ ⚠ same type
CLEC2B p.Asn44Lys Uncertain significance ★ ⚠ same type
CLEC2B p.Cys123Tyr Uncertain significance ★ ⚠ same type
CLEC2B p.Glu53Gly Uncertain significance ★ ⚠ same type
CLEC2B p.Glu53Val 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/clec2b-p-phe115ile (accessed [today's date]).

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