Is CLEC2D p.Asp109Asn (c.325G>A) pathogenic?

CLEC2D p.Asp109Asn (c.325G>A) is classified Uncertain significance in CLEC2D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: likely benign (0.09); Ultra-rare (popmax 0.0416%, afr).

How common is CLEC2D p.Asp109Asn (c.325G>A) in the general population?

CLEC2D p.Asp109Asn (c.325G>A) is ultra-rare (popmax 0.0416%, afr) (gnomAD).

What do computational predictors say about CLEC2D p.Asp109Asn (c.325G>A)?

AlphaMissense predicts likely benign (score 0.09) — an in-silico prediction, not a clinical call.

CLEC2D p.Asp109Asn

c.325G>A · VCV3833920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.09 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0416%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.09	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -5.22	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 -2.6	GERP -3.3
Regional constraint	o/e 0.93	unconstrained · MANE · 25 kb · p 0.33 · regional, not allelic
Overall
CADD	0.11	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 0.0416% African / African-American · 31/74,524 alleles

Filtering AF 0.0301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0262%

Overall 0.00205% 33/1,609,452 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0416%	2,404
Admixed American	0.00168%	59,540
Remaining individualsnot grpmax-eligible	0.00161%	62,284

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: CLEC2D
Protein: p.Asp109Asn
Coding: c.325G>A
MANE Select: NM_013269
Type: single nucleotide variant
Location: chr12:9688054 (GRCh38)
Gene constraint: LOEUF 1.502 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.68 · 6 PDB
Residue 109: the c-type lectin domain; a disulfide bond

Full CLEC2D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC2D c.461+162G>A Uncertain significance ★ same type
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CLEC2D p.Gln117Leu Uncertain significance ★ ⚠ same type
CLEC2D p.Gln154His Uncertain significance ★ ⚠ same type
CLEC2D p.Gly161Arg Uncertain significance ★ ⚠ same type
CLEC2D p.Ile47Val Uncertain significance ★ ⚠ same type
CLEC2D p.Phe102Leu Uncertain significance ★ ⚠ same type
CLEC2D p.Ser14Phe 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/clec2d-p-asp109asn (accessed [today's date]).

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