Is CLEC4E p.Gly155Ser (c.463G>A) pathogenic?

CLEC4E p.Gly155Ser (c.463G>A) is classified Uncertain significance in CLEC4E (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely benign (0.1335); Ultra-rare (popmax 0.0123%, nfe).

How common is CLEC4E p.Gly155Ser (c.463G>A) in the general population?

CLEC4E p.Gly155Ser (c.463G>A) is ultra-rare (popmax 0.0123%, nfe) (gnomAD).

What do computational predictors say about CLEC4E p.Gly155Ser (c.463G>A)?

AlphaMissense predicts likely benign (score 0.1335) — an in-silico prediction, not a clinical call.

CLEC4E p.Gly155Ser

c.463G>A · rs371322474 · VCV3145690

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1335 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0123%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1335	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -7.82	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 0.95
Regional constraint	o/e 0.98	unconstrained · MANE · 6,156 bp · p 0.75 · regional, not allelic
Overall
CADD	12.98	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 0.0123% European (non-Finnish) · 145/1,178,532 alleles

Filtering AF 0.0106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00998%

Overall 0.0093% 150/1,612,046 alleles · ultra-rare exomes 146/1,459,924 · genomes 4/152,122 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0123%	8,128
African / African-American	0.00535%	18,708
Remaining individualsnot grpmax-eligible	0.0016%	62,384

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.Gly155Ser
Coding: c.463G>A
MANE Select: NM_014358
dbSNP: rs371322474
Type: single nucleotide variant
Location: chr12:8536115 (GRCh38)
Gene constraint: LOEUF 1.506 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.57 · 2 PDB
Residue 155: the c-type lectin domain

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

Similar variants

CLEC4E p.Ala102Glu Uncertain significance ★ ⚠ same type
CLEC4E p.Ala102Val Uncertain significance ★ ⚠ same type
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

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-gly155ser (accessed [today's date]).

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