Is CD36 p.Lys223fs (c.667_671del) pathogenic?

CD36 p.Lys223fs (c.667671del) is classified Pathogenic/Likely pathogenic in CD36 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-22). Ultra-rare (popmax 0.0821%, afr); Associated with CD36-related disorder.

What condition is associated with CD36 p.Lys223fs (c.667_671del)?

CD36 p.Lys223fs (c.667_671del) is associated with CD36-related disorder, platelet-type bleeding disorder 10 (ClinVar).

How common is CD36 p.Lys223fs (c.667_671del) in the general population?

CD36 p.Lys223fs (c.667_671del) is ultra-rare (popmax 0.0821%, afr) (gnomAD).

CD36 p.Lys223fs

c.667_671del · rs748431584 · VCV2577330

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0821%, afr)

Conditions

CD36-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.5	GERP 2, phastCons 1
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0821% African / African-American · 61/74,340 alleles

Filtering AF 0.0655% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0596%

Overall 0.00556% 88/1,583,584 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0821%	1,219
South Asian	0.0133%	7,535
Remaining individualsnot grpmax-eligible	0.00488%	20,501
Admixed American	0.00334%	29,965
East Asian	0.00224%	44,596
European (non-Finnish)	0.000781%	128,063

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.Lys223fs
Coding: c.667_671del
MANE Select: NM_001001548
dbSNP: rs748431584
Type: Deletion
Location: chr7:80664459 (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 223: an α-helix

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

Disease context

CD36-related disorder

Also linked: platelet-type bleeding disorder 10

Similar variants

CD36 p.Ile399fs Pathogenic/Likely pathogenic ★★ same condition
CD36 p.Ile410_Ile413del Pathogenic/Likely pathogenic ★★ same condition
CD36 p.Lys213fs Pathogenic/Likely pathogenic ★★ same condition
CD36 c.1200-7_1208del Likely pathogenic ★ same condition
CD36 c.818+1_818+9del Likely pathogenic ★ same condition
CD36 c.(?_-183 Pathogenic ★ same condition
CD36 p.Asn6fs Pathogenic ★ same condition
CD36 p.Gln171fs Likely pathogenic ★ 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-lys223fs (accessed [today's date]).

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