Is CD36 p.Leu449fs (c.1345_1348del) pathogenic?

CD36 p.Leu449fs (c.13451348del) is classified Uncertain significance in CD36 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-04). Ultra-rare (popmax 0.0329%, mid); Associated with platelet-type bleeding disorder 10.

What condition is associated with CD36 p.Leu449fs (c.1345_1348del)?

CD36 p.Leu449fs (c.1345_1348del) is associated with platelet-type bleeding disorder 10 (ClinVar).

How common is CD36 p.Leu449fs (c.1345_1348del) in the general population?

CD36 p.Leu449fs (c.1345_1348del) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

CD36 p.Leu449fs

c.1345_1348del · rs1261881244 · VCV3067875

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

platelet-type bleeding disorder 10

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 14 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 0.83, phastCons 0.98
Overall
CADD	32.0	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 0.0329% Middle Eastern · 2/6,070 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000373% 6/1,610,318 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,035
Remaining individualsnot grpmax-eligible	0.0016%	62,332
Finnishnot grpmax-eligible	0.00156%	63,960
African / African-American	0.00134%	74,824
European (non-Finnish)	8.5e-05%	1,177,110

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.Leu449fs
Coding: c.1345_1348del
MANE Select: NM_001001548
dbSNP: rs1261881244
Type: Deletion
Location: chr7:80674072 (GRCh38)
Gene constraint: LOEUF 1.953 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 94.14 · 1 PDB

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.Ile399fs Pathogenic/Likely pathogenic ★★ same condition
CD36 p.Ile410_Ile413del Pathogenic/Likely pathogenic ★★ same condition
CD36 p.Lys213fs Pathogenic/Likely pathogenic ★★ same condition
CD36 p.Lys223fs Pathogenic/Likely pathogenic ★★ same condition
CD36 c.818+1_818+9del Likely pathogenic ★ same condition
CD36 c.(?_-183 Pathogenic ★ same condition
CD36 p.Gln171fs Likely pathogenic ★ same condition
CD36 p.Lys36fs 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-leu449fs (accessed [today's date]).

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