Is CLEC2A p.Ser150Arg (c.450T>G) pathogenic?

CLEC2A p.Ser150Arg (c.450T>G) is classified Uncertain significance in CLEC2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely pathogenic (0.8555); Very rare (popmax 0.00685%, afr).

How common is CLEC2A p.Ser150Arg (c.450T>G) in the general population?

CLEC2A p.Ser150Arg (c.450T>G) is very rare (popmax 0.00685%, afr) (gnomAD).

What do computational predictors say about CLEC2A p.Ser150Arg (c.450T>G)?

AlphaMissense predicts likely pathogenic (score 0.8555) — an in-silico prediction, not a clinical call.

CLEC2A p.Ser150Arg

c.450T>G · VCV4654283

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8555 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00685%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8555	likely pathogenic
REVEL	0.024	moderately benign-leaning
SaProt	LLR -7.09	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP 1.4
Regional constraint	o/e 0.91	unconstrained · MANE · 19 kb · p 0.21 · regional, not allelic
Overall
CADD	10.94	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 0.00685% African / African-American · 5/73,020 alleles

Filtering AF 0.0026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00165%

Overall 0.000323% 5/1,549,778 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: CLEC2A
Protein: p.Ser150Arg
Coding: c.450T>G
MANE Select: NM_001130711
Type: single nucleotide variant
Location: chr12:9913641 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 88.23 · 1 PDB
Residue 150: 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-ser150arg (accessed [today's date]).

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