Is CLEC4D p.Ser32Gly (c.94A>G) pathogenic?

CLEC4D p.Ser32Gly (c.94A>G) is classified Benign in CLEC4D (ClinVar, Multiple submitters, 2 submitters; last evaluated 2016-03-29). AlphaMissense: likely benign (0.056); Common (popmax 56.9%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CLEC4D p.Ser32Gly (c.94A>G)?

AlphaMissense predicts likely benign (score 0.056) — an in-silico prediction, not a clinical call.

CLEC4D p.Ser32Gly

Q: How common is CLEC4D p.Ser32Gly (c.94A>G) in the general population?

CLEC4D p.Ser32Gly (c.94A>G) is common (popmax 56.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.94A>G · rs4304840 · VCV402542

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.056 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 56.9%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.056	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -7.37	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 0.079
Regional constraint	o/e 1.11	unconstrained · MANE · 7,535 bp · p 0.08 · regional, not allelic
Overall
CADD	0.136	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 56.9% African / African-American · 40,573/71,320 alleles

Filtering AF 56.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 56.2%

Overall 23.2% 340,025/1,467,864 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	56.9%	2
Middle Eastern	40.1%	2
Ashkenazi Jewishnot grpmax-eligible	26.8%	4
Remaining individualsnot grpmax-eligible	24.4%	4
South Asian	23%	4
European (non-Finnish)	21.5%	5
Finnishnot grpmax-eligible	20.9%	5
Amishnot grpmax-eligible	18.5%	5
Admixed American	17.2%	6
East Asian	12.9%	8

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: CLEC4D
Protein: p.Ser32Gly
Coding: c.94A>G
MANE Select: NM_080387
dbSNP: rs4304840
Type: single nucleotide variant
Location: chr12:8515301 (GRCh38)
Gene constraint: LOEUF 1.613 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.58 · 2 PDB
Residue 32: a UniProt-annotated variant site (in)

Full CLEC4D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC4D p.Ala117Ser Uncertain significance ★ ⚠ same type
CLEC4D p.Ala126Thr Uncertain significance ★ ⚠ same type
CLEC4D p.Ala37Glu Uncertain significance ★ ⚠ same type
CLEC4D p.Ala90Gly Uncertain significance ★ ⚠ same type
CLEC4D p.Arg110Ser Uncertain significance ★ ⚠ same type
CLEC4D p.Arg138Trp Uncertain significance ★ ⚠ same type
CLEC4D p.Arg155Cys Uncertain significance ★ ⚠ same type
CLEC4D p.Arg205Thr 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/clec4d-p-ser32gly (accessed [today's date]).

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