Is CLEC2D p.Phe102Leu (c.304T>C) pathogenic?

CLEC2D p.Phe102Leu (c.304T>C) is classified Uncertain significance in CLEC2D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-08). AlphaMissense: likely pathogenic (0.9672); Very rare (popmax 6.85e-05%).

How common is CLEC2D p.Phe102Leu (c.304T>C) in the general population?

CLEC2D p.Phe102Leu (c.304T>C) is very rare (popmax 6.85e-05%) (gnomAD).

What do computational predictors say about CLEC2D p.Phe102Leu (c.304T>C)?

AlphaMissense predicts likely pathogenic (score 0.9672) — an in-silico prediction, not a clinical call.

CLEC2D p.Phe102Leu

c.304T>C · VCV3493570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9672 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9672	likely pathogenic · top 8% in CLEC2D
REVEL	0.208	benign-leaning
SaProt	LLR -11.49	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 0.13	GERP 1.6
Regional constraint	o/e 0.93	unconstrained · MANE · 25 kb · p 0.33 · regional, not allelic
Overall
CADD	19.12	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 6.85e-05%

Overall 6.85e-05% 1/1,460,108 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: CLEC2D
Protein: p.Phe102Leu
Coding: c.304T>C
MANE Select: NM_013269
Type: single nucleotide variant
Location: chr12:9688033 (GRCh38)
Gene constraint: LOEUF 1.502 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.68 · 6 PDB
Residue 102: an α-helix; the c-type lectin domain

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.Gly161Arg Uncertain significance ★ ⚠ same type
CLEC2D p.Ile47Val 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-phe102leu (accessed [today's date]).

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