Is CD36 p.Val194Phe (c.580G>T) pathogenic?

CD36 p.Val194Phe (c.580G>T) is classified Uncertain significance in CD36 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-27). AlphaMissense: likely benign (0.1515); Ultra-rare (popmax 0.0227%, afr).

How common is CD36 p.Val194Phe (c.580G>T) in the general population?

CD36 p.Val194Phe (c.580G>T) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about CD36 p.Val194Phe (c.580G>T)?

AlphaMissense predicts likely benign (score 0.1515) — an in-silico prediction, not a clinical call.

CD36 p.Val194Phe

c.580G>T · rs760233317 · VCV2257561

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1515 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1515	likely benign
REVEL	0.326	indeterminate
SaProt	LLR -9.58	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.20	donor loss · deltas
Constraint at this position
Conservation	phyloP -7	GERP -3.3
Regional constraint	o/e 1.47	unconstrained · MANE · 27 kb · p 5.1e-29 · regional, not allelic
Overall
CADD	0.071	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 0.0227% African / African-American · 17/74,884 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00118% 19/1,613,514 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,405
Remaining individualsnot grpmax-eligible	0.0032%	31,231

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.Val194Phe
Coding: c.580G>T
MANE Select: NM_001001548
dbSNP: rs760233317
Type: single nucleotide variant
Location: chr7:80663140 (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

Similar variants

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
CD36 p.Arg292Ile 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-val194phe (accessed [today's date]).

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