Is CD36 p.Glu418Asp (c.1254G>T) pathogenic?

CD36 p.Glu418Asp (c.1254G>T) is classified Uncertain significance in CD36 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-08-28). AlphaMissense: likely pathogenic (0.9735); Very rare (popmax 0.00271%, afr).

How common is CD36 p.Glu418Asp (c.1254G>T) in the general population?

CD36 p.Glu418Asp (c.1254G>T) is very rare (popmax 0.00271%, afr) (gnomAD).

What do computational predictors say about CD36 p.Glu418Asp (c.1254G>T)?

AlphaMissense predicts likely pathogenic (score 0.9735) — an in-silico prediction, not a clinical call.

CD36 p.Glu418Asp

c.1254G>T · VCV3366532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9735 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9735	likely pathogenic · top 6% in CD36
REVEL	0.667	pathogenic-leaning
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	Δ0.61	donor loss · deltas
Pangolin	Δ0.42	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.4	GERP 2, phastCons 1
Regional constraint	o/e 1.47	unconstrained · MANE · 27 kb · p 5.1e-29 · regional, not allelic
Overall
CADD	35.0	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 0.00271% African / African-American · 2/73,762 alleles

Filtering AF 0.00045% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000168%

Overall 0.000192% 3/1,559,962 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00271%	36,881
Admixed American	0.00167%	59,818

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.Glu418Asp
Coding: c.1254G>T
MANE Select: NM_001001548
Type: single nucleotide variant
Location: chr7:80673409 (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 418: a β-strand

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

Similar variants

CD36 p.Glu418Lys Uncertain significance ★ ⚠ same residue
CD36 c.1254+1G>A Likely pathogenic ★★ same type
CD36 c.430-2A>G Likely pathogenic ★★ same type
CD36 p.Cys243Ter Pathogenic ★★ same type
CD36 p.Leu381Ter Pathogenic/Likely pathogenic ★★ same type
CD36 p.Tyr62Ter Likely pathogenic ★★ same type
CD36 c.-27C>T Uncertain significance ★★ same type
CD36 p.Ala427Ser Uncertain significance ★★ ⚠ same type

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-glu418asp (accessed [today's date]).

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