Is CLEC4M p.Ala145Val (c.434C>T) pathogenic?

CLEC4M p.Ala145Val (c.434C>T) is classified Uncertain significance in CLEC4M (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-23). AlphaMissense: ambiguous (0.3771); Very rare (popmax 0.00534%, afr).

How common is CLEC4M p.Ala145Val (c.434C>T) in the general population?

CLEC4M p.Ala145Val (c.434C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CLEC4M p.Ala145Val (c.434C>T)?

AlphaMissense predicts ambiguous (score 0.3771) — an in-silico prediction, not a clinical call.

CLEC4M p.Ala145Val

c.434C>T · VCV3267701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3771	ambiguous
REVEL	0.036	moderately benign-leaning
SaProt	LLR -10.75	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2
Regional constraint	o/e 0.23	constrained · MANE · 317 bp · p 1.7e-11 · regional, not allelic
Overall
CADD	8.874	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 0.00534% African / African-American · 2/37,424 alleles

Filtering AF 0.000885% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000331%

Overall 0.000526% 3/570,422 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,712
Remaining individualsnot grpmax-eligible	0.00353%	28,360

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.Ala145Val
Coding: c.434C>T
MANE Select: NM_014257
Type: single nucleotide variant
Location: chr19:7765857 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.77 · 7 PDB
Residue 145: the '7 x approximate tandem repeats' region

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

Similar variants

CLEC4M p.Ala237Thr Uncertain significance ★ ⚠ same type
CLEC4M p.Ala295Val Uncertain significance ★ ⚠ same type
CLEC4M p.Ala393Val 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-ala145val (accessed [today's date]).

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