Is CLEC2B p.Leu34Phe (c.102A>C) pathogenic?

CLEC2B p.Leu34Phe (c.102A>C) is classified Likely benign in CLEC2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.0652); Very rare (popmax 0.00951%, nfe).

How common is CLEC2B p.Leu34Phe (c.102A>C) in the general population?

CLEC2B p.Leu34Phe (c.102A>C) is very rare (popmax 0.00951%, nfe) (gnomAD).

What do computational predictors say about CLEC2B p.Leu34Phe (c.102A>C)?

AlphaMissense predicts likely benign (score 0.0652) — an in-silico prediction, not a clinical call.

CLEC2B p.Leu34Phe

c.102A>C · VCV4654286

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0652 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00951%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0652	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -7.59	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 0.92	GERP -2.3, phastCons 0.27
Regional constraint	o/e 0.91	unconstrained · MANE · 9,268 bp · p 0.23 · regional, not allelic
Overall
CADD	0.48	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 0.00951% European (non-Finnish) · 112/1,177,478 alleles

Filtering AF 0.00806% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00754%

Overall 0.00733% 118/1,610,596 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00951%	10,513
Remaining individualsnot grpmax-eligible	0.00802%	12,466
African / African-American	0.00134%	74,782

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.Leu34Phe
Coding: c.102A>C
MANE Select: NM_005127
Type: single nucleotide variant
Location: chr12:9857609 (GRCh38)
Gene constraint: LOEUF 1.404 · pLI 0.52 (gnomAD)
Structure: AlphaFold pLDDT 92.25

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-leu34phe (accessed [today's date]).

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