Is CLEC2A p.Trp137Ter (c.411G>A) pathogenic?

CLEC2A p.Trp137Ter (c.411G>A) is classified Likely benign in CLEC2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Rare (popmax 0.972%, afr).

How common is CLEC2A p.Trp137Ter (c.411G>A) in the general population?

CLEC2A p.Trp137Ter (c.411G>A) is rare (popmax 0.972%, afr) (gnomAD).

CLEC2A p.Trp137Ter

c.411G>A · rs142033208 · VCV2642698

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.972%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.70 · evaluated, not missing
Pangolin	Δ0.20	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -0.52	GERP 1.4, phastCons 0.006
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.972% African / African-American · 707/72,706 alleles

Filtering AF 0.913% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.889%

Overall 0.0562% 865/1,538,826 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.972%	103
Middle Eastern	0.117%	851
Admixed American	0.0957%	1,045
Remaining individualsnot grpmax-eligible	0.072%	1,390
European (non-Finnish)	0.00508%	19,675
South Asian	0.00241%	41,453

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: CLEC2A
Protein: p.Trp137Ter
Coding: c.411G>A
MANE Select: NM_001130711
dbSNP: rs142033208
Type: single nucleotide variant
Location: chr12:9913680 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 88.23 · 1 PDB
Residue 137: the c-type lectin domain; a disulfide bond

Full CLEC2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KLRF2 p.Thr176Ser Uncertain significance ★★ ⚠ same type
CLEC2A p.Ala109Thr Uncertain significance ★ ⚠ same type
CLEC2A p.Ala81Gly Uncertain significance ★ ⚠ same type
CLEC2A p.Arg7Trp Uncertain significance ★ ⚠ same type
CLEC2A p.Asp101Glu Uncertain significance ★ ⚠ same type
CLEC2A p.Cys58Ser Uncertain significance ★ ⚠ same type
CLEC2A p.Cys58Tyr Uncertain significance ★ ⚠ same type
CLEC2A p.Gly110Val 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/clec2a-p-trp137ter (accessed [today's date]).

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