Is CLEC4E p.Arg189Lys (c.566G>A) pathogenic?

CLEC4E p.Arg189Lys (c.566G>A) is classified Uncertain significance in CLEC4E (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely benign (0.0808); Very rare (popmax 0.00223%, eas).

How common is CLEC4E p.Arg189Lys (c.566G>A) in the general population?

CLEC4E p.Arg189Lys (c.566G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CLEC4E p.Arg189Lys (c.566G>A)?

AlphaMissense predicts likely benign (score 0.0808) — an in-silico prediction, not a clinical call.

CLEC4E p.Arg189Lys

c.566G>A · rs2136396493 · VCV3145692

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0808 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0808	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -5.12	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 -0.075
Regional constraint	o/e 0.98	unconstrained · MANE · 6,156 bp · p 0.75 · regional, not allelic
Overall
CADD	5.276	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 0.00223% East Asian · 1/44,872 alleles

Overall 6.84e-05% 1/1,461,824 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: CLEC4E
Protein: p.Arg189Lys
Coding: c.566G>A
MANE Select: NM_014358
dbSNP: rs2136396493
Type: single nucleotide variant
Location: chr12:8534732 (GRCh38)
Gene constraint: LOEUF 1.506 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.57 · 2 PDB
Residue 189: a disulfide bond; 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.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-arg189lys (accessed [today's date]).

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