Is CLEC2D p.Ser14Phe (c.41C>T) pathogenic?

CLEC2D p.Ser14Phe (c.41C>T) is classified Uncertain significance in CLEC2D (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: likely benign (0.1019); Very rare (popmax 0.00534%, afr).

How common is CLEC2D p.Ser14Phe (c.41C>T) in the general population?

CLEC2D p.Ser14Phe (c.41C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CLEC2D p.Ser14Phe (c.41C>T)?

AlphaMissense predicts likely benign (score 0.1019) — an in-silico prediction, not a clinical call.

CLEC2D p.Ser14Phe

c.41C>T · rs369446619 · VCV2520801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1019 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1019	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -8.61	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 -0.84	GERP -1.4
Regional constraint	o/e 0.93	unconstrained · MANE · 25 kb · p 0.33 · regional, not allelic
Overall
CADD	5.707	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 0.00534% African / African-American · 4/74,858 alleles

Filtering AF 0.00418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00415% 67/1,613,548 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,715
European (non-Finnish)	0.00526%	19,027
Remaining individualsnot grpmax-eligible	0.0016%	62,462

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.Ser14Phe
Coding: c.41C>T
MANE Select: NM_013269
dbSNP: rs369446619
Type: single nucleotide variant
Location: chr12:9669775 (GRCh38)
Gene constraint: LOEUF 1.502 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.68 · 6 PDB

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.Phe102Leu 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-ser14phe (accessed [today's date]).

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