Is CLEC4D p.His170Gln (c.510T>A) pathogenic?

CLEC4D p.His170Gln (c.510T>A) is classified Uncertain significance in CLEC4D (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). AlphaMissense: likely benign (0.2148); Ultra-rare (popmax 0.0469%, amr).

How common is CLEC4D p.His170Gln (c.510T>A) in the general population?

CLEC4D p.His170Gln (c.510T>A) is ultra-rare (popmax 0.0469%, amr) (gnomAD).

What do computational predictors say about CLEC4D p.His170Gln (c.510T>A)?

AlphaMissense predicts likely benign (score 0.2148) — an in-silico prediction, not a clinical call.

CLEC4D p.His170Gln

c.510T>A · rs1037179933 · VCV3145682

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2148 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0469%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2148	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.33	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 0.53	phastCons 0.003
Regional constraint	o/e 1.11	unconstrained · MANE · 7,535 bp · p 0.08 · regional, not allelic
Overall
CADD	16.08	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

Grpmax group 0.0469% Admixed American · 28/59,688 alleles

Filtering AF 0.0333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0288%

Overall 0.00223% 36/1,612,480 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0469%	2,132
Remaining individualsnot grpmax-eligible	0.00801%	12,479
African / African-American	0.00134%	74,830
European (non-Finnish)	0.00017%	589,637

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.His170Gln
Coding: c.510T>A
MANE Select: NM_080387
dbSNP: rs1037179933
Type: single nucleotide variant
Location: chr12:8521133 (GRCh38)
Gene constraint: LOEUF 1.613 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.58 · 2 PDB
Residue 170: a disulfide bond; the c-type lectin domain

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

Similar variants

CLEC4D p.His170Arg Uncertain significance ★ ⚠ same residue
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

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-his170gln (accessed [today's date]).

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