Is CLEC4M p.Phe351Ser (c.1052T>C) pathogenic?

CLEC4M p.Phe351Ser (c.1052T>C) is classified Uncertain significance in CLEC4M (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely pathogenic (0.6361); Very rare (popmax 8.48e-05%, nfe).

How common is CLEC4M p.Phe351Ser (c.1052T>C) in the general population?

CLEC4M p.Phe351Ser (c.1052T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CLEC4M p.Phe351Ser (c.1052T>C)?

AlphaMissense predicts likely pathogenic (score 0.6361) — an in-silico prediction, not a clinical call.

CLEC4M p.Phe351Ser

c.1052T>C · rs2034395187 · VCV3145708

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6361 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6361	likely pathogenic
REVEL	0.047	moderately benign-leaning
SaProt	LLR -8.34	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	phastCons 0.006
Regional constraint	o/e 0.93	unconstrained · MANE · 2,866 bp · p 0.28 · regional, not allelic
Overall
CADD	19.01	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 8.48e-05% European (non-Finnish) · 1/1,179,850 alleles

Overall 6.84e-05% 1/1,461,630 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: CLEC4M
Protein: p.Phe351Ser
Coding: c.1052T>C
MANE Select: NM_014257
dbSNP: rs2034395187
Type: single nucleotide variant
Location: chr19:7768840 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.77 · 7 PDB
Residue 351: the c-type lectin domain; a disulfide bond; an α-helix

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.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

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-phe351ser (accessed [today's date]).

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