Is SLC2A4 p.Arg285Trp (c.853C>T) pathogenic?

SLC2A4 p.Arg285Trp (c.853C>T) is classified Uncertain significance in SLC2A4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-15). AlphaMissense: likely benign (0.1575); Ultra-rare (popmax 0.0999%, afr).

How common is SLC2A4 p.Arg285Trp (c.853C>T) in the general population?

SLC2A4 p.Arg285Trp (c.853C>T) is ultra-rare (popmax 0.0999%, afr) (gnomAD).

What do computational predictors say about SLC2A4 p.Arg285Trp (c.853C>T)?

AlphaMissense predicts likely benign (score 0.1575) — an in-silico prediction, not a clinical call.

SLC2A4 p.Arg285Trp

c.853C>T · rs140743598 · VCV3164147

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1575 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0999%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1575	likely benign
REVEL	0.783	moderately pathogenic-leaning
SaProt	LLR -7.69	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 2.3, phastCons 0.99
Regional constraint	o/e 0.82	unconstrained · MANE · 4,691 bp · p 4.3e-06 · regional, not allelic
Overall
CADD	26.7	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 0.0999% African / African-American · 75/75,066 alleles

Filtering AF 0.0817% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.075%

Overall 0.0101% 163/1,614,204 alleles · ultra-rare exomes 123/1,461,838 · genomes 40/152,366 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0999%	1,001
Middle Eastern	0.0495%	2,021
Finnishnot grpmax-eligible	0.0125%	8,001
Remaining individualsnot grpmax-eligible	0.0112%	8,930
South Asian	0.00988%	10,120
Admixed American	0.00833%	12,007
European (non-Finnish)	0.00466%	21,455
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

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: SLC2A4
Protein: p.Arg285Trp
Coding: c.853C>T
MANE Select: NM_001042
dbSNP: rs140743598
Type: single nucleotide variant
Location: chr17:7284610 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.12 · 2 PDB
Residue 285: an α-helix

Full SLC2A4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC2A4 p.Arg285Gln Uncertain significance ★ ⚠ same residue
SLC2A4 p.Ile186= Benign ★★ same type
SLC2A4 p.Ala119Val Uncertain significance ★ same type
SLC2A4 p.Ala164Thr Uncertain significance ★ same type
SLC2A4 p.Ala171Thr Uncertain significance ★ ⚠ same type
SLC2A4 p.Ala251Ser Uncertain significance ★ ⚠ same type
SLC2A4 p.Ala347Val Uncertain significance ★ ⚠ same type
SLC2A4 p.Ala454Val 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/slc2a4-p-arg285trp (accessed [today's date]).

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