Is SLC3A2 p.Phe258Val (c.772T>G) pathogenic?

SLC3A2 p.Phe258Val (c.772T>G) is classified Uncertain significance in SLC3A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-19). AlphaMissense: likely benign (0.0781); Absent from gnomAD v4.1.

How common is SLC3A2 p.Phe258Val (c.772T>G) in the general population?

SLC3A2 p.Phe258Val (c.772T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SLC3A2 p.Phe258Val (c.772T>G)?

AlphaMissense predicts likely benign (score 0.0781) — an in-silico prediction, not a clinical call.

SLC3A2 p.Phe258Val

c.772T>G · rs2539519908 · VCV2312637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0781 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0781	likely benign
REVEL	0.468	indeterminate
SaProt	LLR -6.10	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.45	GERP -3.7
Regional constraint	o/e 0.92	unconstrained · MANE · 4,495 bp · p 0.075 · regional, not allelic
Overall
CADD	14.96	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F359V vs ClinVar F258V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SLC3A2
Protein: p.Phe258Val
Coding: c.772T>G
MANE Select: NM_001013251
dbSNP: rs2539519908
Type: single nucleotide variant
Location: chr11:62884644 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.01 · 44 PDB
Residue 258: an α-helix

Full SLC3A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC3A2 c.301+3G>A Benign ★★ same type
SLC3A2 p.Arg338Met Likely benign ★★ ⚠ same type
SLC3A2 p.Leu435= Benign ★★ same type
SLC3A2 p.Lys491Gln Benign ★★ same type
SLC3A2 p.Pro415Ser Benign/Likely benign ★★ same type
SLC3A2 p.Ala346Ser Uncertain significance ★ ⚠ same type
SLC3A2 p.Ala346Thr Uncertain significance ★ ⚠ same type
SLC3A2 p.Ala492Gly 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/slc3a2-p-phe258val (accessed [today's date]).

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