Is CLEC4G p.Ser175Pro (c.523T>C) pathogenic?

CLEC4G p.Ser175Pro (c.523T>C) is classified Uncertain significance in CLEC4G (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: likely pathogenic (0.8484); Absent from gnomAD v4.1.

How common is CLEC4G p.Ser175Pro (c.523T>C) in the general population?

CLEC4G p.Ser175Pro (c.523T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLEC4G p.Ser175Pro (c.523T>C)?

AlphaMissense predicts likely pathogenic (score 0.8484) — an in-silico prediction, not a clinical call.

CLEC4G p.Ser175Pro

c.523T>C · VCV4229793

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8484 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8484	likely pathogenic · top 8% in CLEC4G
REVEL	0.318	indeterminate
SaProt	LLR -15.01	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 2,733 bp · p 0.89 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: CLEC4G
Protein: p.Ser175Pro
Coding: c.523T>C
MANE Select: NM_198492
Type: single nucleotide variant
Location: chr19:7730123 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.39
Residue 175: the c-type lectin domain

Full CLEC4G gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC4G p.Ala196Ser Uncertain significance ★ ⚠ same type
CLEC4G p.Ala258Val Uncertain significance ★ ⚠ same type
CLEC4G p.Ala276Thr Uncertain significance ★ ⚠ same type
CLEC4G p.Arg106His Uncertain significance ★ ⚠ same type
CLEC4G p.Arg127His Uncertain significance ★ ⚠ same type
CLEC4G p.Arg226Lys Uncertain significance ★ ⚠ same type
CLEC4G p.Arg23Cys Uncertain significance ★ ⚠ same type
CLEC4G p.Asn274Ser 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/clec4g-p-ser175pro (accessed [today's date]).

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