Is CD36 p.Val214Ile (c.640G>A) pathogenic?

CD36 p.Val214Ile (c.640G>A) is classified Uncertain significance in CD36 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.1014); Very rare (popmax 0.00096%, nfe); Associated with platelet-type bleeding disorder 10.

What condition is associated with CD36 p.Val214Ile (c.640G>A)?

CD36 p.Val214Ile (c.640G>A) is associated with platelet-type bleeding disorder 10 (ClinVar).

How common is CD36 p.Val214Ile (c.640G>A) in the general population?

CD36 p.Val214Ile (c.640G>A) is very rare (popmax 0.00096%, nfe) (gnomAD).

What do computational predictors say about CD36 p.Val214Ile (c.640G>A)?

AlphaMissense predicts likely benign (score 0.1014) — an in-silico prediction, not a clinical call.

CD36 p.Val214Ile

c.640G>A · rs190735330 · VCV360760

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1014 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00096%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

platelet-type bleeding disorder 10

Computational evidence

Protein change
AlphaMissense	0.1014	likely benign
REVEL	0.241	benign-leaning
SaProt	LLR -7.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.5	GERP 2, phastCons 1
Regional constraint	o/e 1.47	unconstrained · MANE · 27 kb · p 5.1e-29 · regional, not allelic
Overall
CADD	21.4	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

Grpmax group 0.00096% European (non-Finnish) · 11/1,146,250 alleles

Filtering AF 0.000515% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000376%

Overall 0.000761% 12/1,576,606 alleles · very rare exomes 11/1,424,422 · genomes 1/152,184 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00163%	61,262
European (non-Finnish)grpmax	0.00096%	104,205

Remaining individuals 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.Val214Ile
Coding: c.640G>A
MANE Select: NM_001001548
dbSNP: rs190735330
Type: single nucleotide variant
Location: chr7:80664436 (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 214: 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 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-val214ile (accessed [today's date]).

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