Is CLEC4M p.Ala393Val (c.1178C>T) pathogenic?

CLEC4M p.Ala393Val (c.1178C>T) is classified Uncertain significance in CLEC4M (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-12). AlphaMissense: likely benign (0.2458); Ultra-rare (popmax 0.0445%, eas).

How common is CLEC4M p.Ala393Val (c.1178C>T) in the general population?

CLEC4M p.Ala393Val (c.1178C>T) is ultra-rare (popmax 0.0445%, eas) (gnomAD).

What do computational predictors say about CLEC4M p.Ala393Val (c.1178C>T)?

AlphaMissense predicts likely benign (score 0.2458) — an in-silico prediction, not a clinical call.

CLEC4M p.Ala393Val

c.1178C>T · rs764629639 · VCV3145709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2458 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0445%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2458	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -12.14	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -3.3
Regional constraint	o/e 0.93	unconstrained · MANE · 2,866 bp · p 0.28 · regional, not allelic
Overall
CADD	12.55	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 0.0445% East Asian · 20/44,900 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.00143% 23/1,613,966 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0445%	2,245
Middle Eastern	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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: CLEC4M
Protein: p.Ala393Val
Coding: c.1178C>T
MANE Select: NM_014257
dbSNP: rs764629639
Type: single nucleotide variant
Location: chr19:7768966 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.77 · 7 PDB
Residue 393: a disulfide bond

Full CLEC4M gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC4M p.Ala145Val Uncertain significance ★ ⚠ same type
CLEC4M p.Ala237Thr Uncertain significance ★ ⚠ same type
CLEC4M p.Ala295Val Uncertain significance ★ ⚠ same type
CLEC4M p.Ala394Gly Uncertain significance ★ ⚠ same type
CLEC4M p.Ala62Gly Uncertain significance ★ ⚠ same type
CLEC4M p.Arg141Trp Uncertain significance ★ ⚠ same type
CLEC4M p.Arg353Trp Uncertain significance ★ ⚠ same type
CLEC4M p.Asp271Val 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/clec4m-p-ala393val (accessed [today's date]).

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