Is CLEC4M p.Ser245Phe (c.734C>T) pathogenic?

CLEC4M p.Ser245Phe (c.734C>T) is classified Uncertain significance in CLEC4M (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-29). AlphaMissense: ambiguous (0.3522); Absent from gnomAD v4.1.

How common is CLEC4M p.Ser245Phe (c.734C>T) in the general population?

CLEC4M p.Ser245Phe (c.734C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLEC4M p.Ser245Phe (c.734C>T)?

AlphaMissense predicts ambiguous (score 0.3522) — an in-silico prediction, not a clinical call.

CLEC4M p.Ser245Phe

c.734C>T · rs764498380 · VCV3145714

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3522 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3522	ambiguous
REVEL	0.023	moderately benign-leaning
SaProt	LLR -11.32	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 0.39	phastCons 0.01
Regional constraint	o/e 0.93	unconstrained · MANE · 2,866 bp · p 0.28 · regional, not allelic
Overall
CADD	16.38	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLEC4M
Protein: p.Ser245Phe
Coding: c.734C>T
MANE Select: NM_014257
dbSNP: rs764498380
Type: single nucleotide variant
Location: chr19:7766157 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.77 · 7 PDB
Residue 245: 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.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-ser245phe (accessed [today's date]).

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