Is CD36 p.Ser125Leu (c.374C>T) pathogenic?

CD36 p.Ser125Leu (c.374C>T) is classified Uncertain significance in CD36 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.1409); Absent from gnomAD v4.1; Associated with platelet-type bleeding disorder 10.

What condition is associated with CD36 p.Ser125Leu (c.374C>T)?

CD36 p.Ser125Leu (c.374C>T) is associated with platelet-type bleeding disorder 10 (ClinVar).

How common is CD36 p.Ser125Leu (c.374C>T) in the general population?

CD36 p.Ser125Leu (c.374C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD36 p.Ser125Leu (c.374C>T)?

AlphaMissense predicts likely benign (score 0.1409) — an in-silico prediction, not a clinical call.

CD36 p.Ser125Leu

c.374C>T · rs886062453 · VCV360755

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1409 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

platelet-type bleeding disorder 10

Computational evidence

Protein change
AlphaMissense	0.1409	likely benign
REVEL	0.319	indeterminate
SaProt	LLR -9.23	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.8, phastCons 0.27
Regional constraint	o/e 1.47	unconstrained · MANE · 27 kb · p 5.1e-29 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: CD36
Protein: p.Ser125Leu
Coding: c.374C>T
MANE Select: NM_001001548
dbSNP: rs886062453
Type: single nucleotide variant
Location: chr7:80661155 (GRCh38)
Gene constraint: LOEUF 1.953 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 94.14 · 1 PDB
Residue 125: an α-helix

Full CD36 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

platelet-type bleeding disorder 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD36 c.1254+1G>A Likely pathogenic ★★ same condition
CD36 c.430-2A>G Likely pathogenic ★★ same condition
CD36 p.Cys243Ter Pathogenic ★★ same condition
CD36 p.Leu381Ter Pathogenic/Likely pathogenic ★★ same condition
CD36 p.Tyr62Ter Likely pathogenic ★★ same condition
CD36 c.-27C>T Uncertain significance ★★ same condition
CD36 p.Ala427Ser Uncertain significance ★★ ⚠ same condition
CD36 p.Arg292Ile Uncertain significance ★★ ⚠ same condition

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/cd36-p-ser125leu (accessed [today's date]).

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