Is CD36 p.Pro375Leu (c.1124C>T) pathogenic?

CD36 p.Pro375Leu (c.1124C>T) is classified Uncertain significance in CD36 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-04). AlphaMissense: likely pathogenic (0.8076); Ultra-rare (popmax 0.0209%, sas); Associated with platelet-type bleeding disorder 10.

What condition is associated with CD36 p.Pro375Leu (c.1124C>T)?

CD36 p.Pro375Leu (c.1124C>T) is associated with platelet-type bleeding disorder 10 (ClinVar).

How common is CD36 p.Pro375Leu (c.1124C>T) in the general population?

CD36 p.Pro375Leu (c.1124C>T) is ultra-rare (popmax 0.0209%, sas) (gnomAD).

What do computational predictors say about CD36 p.Pro375Leu (c.1124C>T)?

AlphaMissense predicts likely pathogenic (score 0.8076) — an in-silico prediction, not a clinical call.

CD36 p.Pro375Leu

c.1124C>T · rs747406134 · VCV3062138

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8076 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

platelet-type bleeding disorder 10

Computational evidence

Protein change
AlphaMissense	0.8076	likely pathogenic
REVEL	0.89	moderately pathogenic-leaning
SaProt	LLR -11.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 1.47	unconstrained · MANE · 27 kb · p 5.1e-29 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.0209% South Asian · 19/90,742 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.00181% 29/1,603,944 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0209%	4,776
Middle Eastern	0.0187%	5,336
Admixed American	0.01%	9,974
European (non-Finnish)	0.000256%	390,914

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.Pro375Leu
Coding: c.1124C>T
MANE Select: NM_001001548
dbSNP: rs747406134
Type: single nucleotide variant
Location: chr7:80672039 (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 375: a turn

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-pro375leu (accessed [today's date]).

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