Is CD36 p.Gln74Ter (c.220C>T) pathogenic?

CD36 p.Gln74Ter (c.220C>T) is classified Conflicting classifications of pathogenicity in CD36 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-04-22). Ultra-rare (popmax 0.099%, mid); Associated with malaria, susceptibility to.

What condition is associated with CD36 p.Gln74Ter (c.220C>T)?

CD36 p.Gln74Ter (c.220C>T) is associated with malaria, susceptibility to, platelet-type bleeding disorder 10, coronary heart disease, susceptibility to, 7 (ClinVar).

How common is CD36 p.Gln74Ter (c.220C>T) in the general population?

CD36 p.Gln74Ter (c.220C>T) is ultra-rare (popmax 0.099%, mid) (gnomAD).

CD36 p.Gln74Ter

c.220C>T · rs545489204 · VCV632007

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.099%, mid)

Conditions

malaria, susceptibility to

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 15
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.82	GERP -4.2
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 0.099% Middle Eastern · 6/6,060 alleles

Filtering AF 0.0782% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0723%

Overall 0.00892% 144/1,613,772 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.099%	1,010
South Asian	0.0944%	1,059
East Asian	0.0558%	1,792
Remaining individualsnot grpmax-eligible	0.0272%	3,676
African / African-American	0.00133%	75,008
European (non-Finnish)	0.000763%	131,091

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.Gln74Ter
Coding: c.220C>T
MANE Select: NM_001001548
dbSNP: rs545489204
Type: single nucleotide variant
Location: chr7:80656639 (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 74: an α-helix

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

Disease context

malaria, susceptibility to — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: platelet-type bleeding disorder 10 coronary heart disease, susceptibility to, 7

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-gln74ter (accessed [today's date]).

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