Is CD36 p.Tyr291Cys (c.872A>G) pathogenic?

CD36 p.Tyr291Cys (c.872A>G) is classified Uncertain significance in CD36 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-04-27). AlphaMissense: likely benign (0.3129); Ultra-rare (popmax 0.0658%, mid); Associated with platelet-type bleeding disorder 10.

What condition is associated with CD36 p.Tyr291Cys (c.872A>G)?

CD36 p.Tyr291Cys (c.872A>G) is associated with platelet-type bleeding disorder 10 (ClinVar).

How common is CD36 p.Tyr291Cys (c.872A>G) in the general population?

CD36 p.Tyr291Cys (c.872A>G) is ultra-rare (popmax 0.0658%, mid) (gnomAD).

What do computational predictors say about CD36 p.Tyr291Cys (c.872A>G)?

AlphaMissense predicts likely benign (score 0.3129) — an in-silico prediction, not a clinical call.

CD36 p.Tyr291Cys

c.872A>G · rs200752989 · VCV908991

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3129 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0658%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

platelet-type bleeding disorder 10

Computational evidence

Protein change
AlphaMissense	0.3129	likely benign
REVEL	0.731	pathogenic-leaning
SaProt	LLR -13.23	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.1	GERP -0.63, phastCons 0.66
Regional constraint	o/e 1.47	unconstrained · MANE · 27 kb · p 5.1e-29 · regional, not allelic
Overall
CADD	24.5	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 0.0658% Middle Eastern · 4/6,080 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00843% 136/1,613,146 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.122%	822
Middle Easterngrpmax	0.0658%	1,520
Remaining individualsnot grpmax-eligible	0.00961%	10,407
European (non-Finnish)	0.00729%	13,713
Admixed American	0.00333%	29,993
South Asian	0.0022%	45,533

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr291Cys
Coding: c.872A>G
MANE Select: NM_001001548
dbSNP: rs200752989
Type: single nucleotide variant
Location: chr7:80671030 (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 291: a disulfide bond; a β-strand

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 p.Tyr291His Uncertain significance ★ ⚠ same residue
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

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-tyr291cys (accessed [today's date]).

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