Is CLEC4G p.Asp90Ala (c.269A>C) pathogenic?

CLEC4G p.Asp90Ala (c.269A>C) is classified Likely benign in CLEC4G (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely benign (0.0502); Very rare (popmax 0.00269%, afr).

How common is CLEC4G p.Asp90Ala (c.269A>C) in the general population?

CLEC4G p.Asp90Ala (c.269A>C) is very rare (popmax 0.00269%, afr) (gnomAD).

What do computational predictors say about CLEC4G p.Asp90Ala (c.269A>C)?

AlphaMissense predicts likely benign (score 0.0502) — an in-silico prediction, not a clinical call.

CLEC4G p.Asp90Ala

c.269A>C · VCV4654318

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0502 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0502	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -4.34	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 0.58	GERP -3, phastCons 0.12
Regional constraint	o/e 0.99	unconstrained · MANE · 2,733 bp · p 0.89 · regional, not allelic
Overall
CADD	0.318	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00269% African / African-American · 2/74,438 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00181% 29/1,603,234 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00269%	37,219
European (non-Finnish)	0.0022%	45,358
Finnishnot grpmax-eligible	0.00181%	55,226

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: CLEC4G
Protein: p.Asp90Ala
Coding: c.269A>C
MANE Select: NM_198492
Type: single nucleotide variant
Location: chr19:7731040 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.39

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-asp90ala (accessed [today's date]).

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