Is CLEC4E p.Ala102Glu (c.305C>A) pathogenic?

CLEC4E p.Ala102Glu (c.305C>A) is classified Uncertain significance in CLEC4E (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.1201); Ultra-rare (popmax 0.02%, afr).

How common is CLEC4E p.Ala102Glu (c.305C>A) in the general population?

CLEC4E p.Ala102Glu (c.305C>A) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about CLEC4E p.Ala102Glu (c.305C>A)?

AlphaMissense predicts likely benign (score 0.1201) — an in-silico prediction, not a clinical call.

CLEC4E p.Ala102Glu

c.305C>A · rs201571010 · VCV3145687

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1201 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1201	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -3.13	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 0.8
Regional constraint	o/e 0.98	unconstrained · MANE · 6,156 bp · p 0.75 · regional, not allelic
Overall
CADD	1.724	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 0.02% African / African-American · 15/75,024 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00988%

Overall 0.00112% 18/1,613,994 alleles · ultra-rare exomes 10/1,461,758 · genomes 8/152,236 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	5,002
Admixed American	0.00333%	30,002
Remaining individualsnot grpmax-eligible	0.0016%	62,496

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: CLEC4E
Protein: p.Ala102Glu
Coding: c.305C>A
MANE Select: NM_014358
dbSNP: rs201571010
Type: single nucleotide variant
Location: chr12:8537182 (GRCh38)
Gene constraint: LOEUF 1.506 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.57 · 2 PDB
Residue 102: an α-helix; the c-type lectin domain

Full CLEC4E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC4E p.Ala102Val Uncertain significance ★ ⚠ same residue
CLEC4E p.Arg14Thr Uncertain significance ★ ⚠ same type
CLEC4E p.Arg189Lys Uncertain significance ★ ⚠ same type
CLEC4E p.Asn214Lys Uncertain significance ★ ⚠ same type
CLEC4E p.Asn2His Uncertain significance ★ ⚠ same type
CLEC4E p.Asn70Ser Uncertain significance ★ ⚠ same type
CLEC4E p.Cys52Tyr Uncertain significance ★ ⚠ same type
CLEC4E p.Gln121Arg 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/clec4e-p-ala102glu (accessed [today's date]).

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