Is CLEC4D p.Cys83Gly (c.247T>G) pathogenic?

CLEC4D p.Cys83Gly (c.247T>G) is classified Uncertain significance in CLEC4D (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). AlphaMissense: ambiguous (0.451); Very rare (popmax 0.00501%, amr).

How common is CLEC4D p.Cys83Gly (c.247T>G) in the general population?

CLEC4D p.Cys83Gly (c.247T>G) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about CLEC4D p.Cys83Gly (c.247T>G)?

AlphaMissense predicts ambiguous (score 0.451) — an in-silico prediction, not a clinical call.

CLEC4D p.Cys83Gly

c.247T>G · rs1251648957 · VCV2466403

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.451 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Computational evidence

Protein change
AlphaMissense	0.451	ambiguous
REVEL	0.297	indeterminate
SaProt	LLR -15.77	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 7,535 bp · p 0.08 · regional, not allelic
Overall
CADD	25.0	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 0.00501% Admixed American · 3/59,936 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000186% 3/1,613,798 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: CLEC4D
Protein: p.Cys83Gly
Coding: c.247T>G
MANE Select: NM_080387
dbSNP: rs1251648957
Type: single nucleotide variant
Location: chr12:8519023 (GRCh38)
Gene constraint: LOEUF 1.613 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.58 · 2 PDB
Residue 83: a β-strand

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

Similar variants

CLEC4D p.Ser32Gly Benign ★★ same type
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

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-cys83gly (accessed [today's date]).

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