Is CLEC2A p.Arg7Trp (c.19C>T) pathogenic?

CLEC2A p.Arg7Trp (c.19C>T) is classified Uncertain significance in CLEC2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-19). AlphaMissense: likely benign (0.1721); Very rare (popmax 0.00119%, sas).

How common is CLEC2A p.Arg7Trp (c.19C>T) in the general population?

CLEC2A p.Arg7Trp (c.19C>T) is very rare (popmax 0.00119%, sas) (gnomAD).

What do computational predictors say about CLEC2A p.Arg7Trp (c.19C>T)?

AlphaMissense predicts likely benign (score 0.1721) — an in-silico prediction, not a clinical call.

CLEC2A p.Arg7Trp

c.19C>T · VCV3493562

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1721 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1721	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -8.30	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 -2	GERP -1.1
Regional constraint	o/e 0.91	unconstrained · MANE · 19 kb · p 0.21 · regional, not allelic
Overall
CADD	15.84	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 0.00119% South Asian · 1/84,032 alleles

Overall 0.000143% 2/1,399,622 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00119%	84,032
European (non-Finnish)	8.72e-05%	1,146,928

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.Arg7Trp
Coding: c.19C>T
MANE Select: NM_001130711
Type: single nucleotide variant
Location: chr12:9932311 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 88.23 · 1 PDB

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

Similar variants

KLRF2 p.Tyr7His Uncertain significance ★ ⚠ same residue
KLRF2 p.Thr176Ser Uncertain significance ★★ ⚠ same type
CLEC2A p.Ala109Thr Uncertain significance ★ ⚠ same type
CLEC2A p.Ala81Gly 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-arg7trp (accessed [today's date]).

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