Is CLEC2D p.Gly161Arg (c.481G>A) pathogenic?

CLEC2D p.Gly161Arg (c.481G>A) is classified Uncertain significance in CLEC2D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely pathogenic (0.9601); Very rare (popmax 0.00357%, nfe).

How common is CLEC2D p.Gly161Arg (c.481G>A) in the general population?

CLEC2D p.Gly161Arg (c.481G>A) is very rare (popmax 0.00357%, nfe) (gnomAD).

What do computational predictors say about CLEC2D p.Gly161Arg (c.481G>A)?

AlphaMissense predicts likely pathogenic (score 0.9601) — an in-silico prediction, not a clinical call.

CLEC2D p.Gly161Arg

c.481G>A · VCV4229747

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9601 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00357%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9601	likely pathogenic · top 10% in CLEC2D
REVEL	0.132	moderately benign-leaning
SaProt	LLR -13.74	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.9, phastCons 0.19
Regional constraint	o/e 0.93	unconstrained · MANE · 25 kb · p 0.33 · regional, not allelic
Overall
CADD	20.7	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 0.00357% European (non-Finnish) · 42/1,176,562 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00237%

Overall 0.00267% 43/1,610,088 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00357%	28,013
Remaining individualsnot grpmax-eligible	0.0016%	62,354

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.Gly161Arg
Coding: c.481G>A
MANE Select: NM_013269
Type: single nucleotide variant
Location: chr12:9694779 (GRCh38)
Gene constraint: LOEUF 1.502 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.68 · 6 PDB
Residue 161: 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
CLEC2D c.461+183T>C Uncertain significance ★ same type
CLEC2D p.Asp109Asn Uncertain significance ★ ⚠ same type
CLEC2D p.Gln117Leu Uncertain significance ★ ⚠ same type
CLEC2D p.Gln154His 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-gly161arg (accessed [today's date]).

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