Is CLEC4F p.Glu179Asp (c.537G>C) pathogenic?

CLEC4F p.Glu179Asp (c.537G>C) is classified Uncertain significance in CLEC4F (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). AlphaMissense: likely benign (0.1211); Absent from gnomAD v4.1.

How common is CLEC4F p.Glu179Asp (c.537G>C) in the general population?

CLEC4F p.Glu179Asp (c.537G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLEC4F p.Glu179Asp (c.537G>C)?

AlphaMissense predicts likely benign (score 0.1211) — an in-silico prediction, not a clinical call.

CLEC4F p.Glu179Asp

c.537G>C · rs2466005045 · VCV2334514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1211 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1211	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -8.46	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 1.4	GERP 0.29, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 11 kb · p 0.038 · regional, not allelic
Overall
CADD	11.09	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLEC4F
Protein: p.Glu179Asp
Coding: c.537G>C
MANE Select: NM_173535
dbSNP: rs2466005045
Type: single nucleotide variant
Location: chr2:70816844 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.95

Full CLEC4F gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC4F p.Asn146Ser Benign ★★ same type
CLEC4F p.Thr235Met Benign/Likely benign ★★ ⚠ same type
CLEC4F p.Val369Ala Benign ★★ same type
CLEC4F p.Ala192Thr Uncertain significance ★ ⚠ same type
CLEC4F p.Ala222Thr Uncertain significance ★ ⚠ same type
CLEC4F p.Ala26Thr Uncertain significance ★ ⚠ same type
CLEC4F p.Ala28Gly Uncertain significance ★ ⚠ same type
CLEC4F p.Ala386Gly 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/clec4f-p-glu179asp (accessed [today's date]).

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