Is CLEC4D p.Ala37Glu (c.110C>A) pathogenic?

CLEC4D p.Ala37Glu (c.110C>A) is classified Uncertain significance in CLEC4D (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-30). AlphaMissense: ambiguous (0.3733); Ultra-rare (popmax 0.0208%, sas).

How common is CLEC4D p.Ala37Glu (c.110C>A) in the general population?

CLEC4D p.Ala37Glu (c.110C>A) is ultra-rare (popmax 0.0208%, sas) (gnomAD).

What do computational predictors say about CLEC4D p.Ala37Glu (c.110C>A)?

AlphaMissense predicts ambiguous (score 0.3733) — an in-silico prediction, not a clinical call.

CLEC4D p.Ala37Glu

c.110C>A · rs773508170 · VCV2213708

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3733 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0208%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3733	ambiguous
REVEL	0.148	moderately benign-leaning
SaProt	LLR -9.49	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.6	phastCons 0.12
Regional constraint	o/e 1.11	unconstrained · MANE · 7,535 bp · p 0.08 · regional, not allelic
Overall
CADD	17.68	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 0.0208% South Asian · 18/86,746 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0111%

Overall 0.00136% 19/1,396,432 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0208%	4,819
European (non-Finnish)	0.000102%	982,251

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.Ala37Glu
Coding: c.110C>A
MANE Select: NM_080387
dbSNP: rs773508170
Type: single nucleotide variant
Location: chr12:8515317 (GRCh38)
Gene constraint: LOEUF 1.613 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.58 · 2 PDB

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.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-ala37glu (accessed [today's date]).

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