Is CD36 p.Phe254Leu (c.760T>C) pathogenic?

CD36 p.Phe254Leu (c.760T>C) is classified Pathogenic in CD36 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2002-04-01). AlphaMissense: likely pathogenic (0.9895); Rare (popmax 0.118%, eas); Associated with platelet-type bleeding disorder 10.

What condition is associated with CD36 p.Phe254Leu (c.760T>C)?

CD36 p.Phe254Leu (c.760T>C) is associated with platelet-type bleeding disorder 10 (ClinVar).

How common is CD36 p.Phe254Leu (c.760T>C) in the general population?

CD36 p.Phe254Leu (c.760T>C) is rare (popmax 0.118%, eas) (gnomAD).

What do computational predictors say about CD36 p.Phe254Leu (c.760T>C)?

AlphaMissense predicts likely pathogenic (score 0.9895) — an in-silico prediction, not a clinical call.

CD36 p.Phe254Leu

c.760T>C · rs142186404 · VCV13540

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9895 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.118%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

platelet-type bleeding disorder 10

Computational evidence

Protein change
AlphaMissense	0.9895	likely pathogenic ✓ concordant with ClinVar · top 2% in CD36
REVEL	0.822	moderately pathogenic-leaning
SaProt	LLR -9.71	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 1.47	unconstrained · MANE · 27 kb · p 5.1e-29 · regional, not allelic
Overall
CADD	28.4	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 0.118% East Asian · 53/44,852 alleles

Filtering AF 0.0928% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0837%

Overall 0.00341% 55/1,612,176 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.118%	846
Remaining individualsnot grpmax-eligible	0.0016%	62,430
European (non-Finnish)	8.49e-05%	1,178,350

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: CD36
Protein: p.Phe254Leu
Coding: c.760T>C
MANE Select: NM_001001548
dbSNP: rs142186404
Type: single nucleotide variant
Location: chr7:80669964 (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 254: a disulfide bond; a UniProt-annotated variant site (in pg4d; type i)

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-phe254leu (accessed [today's date]).

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