Is SLC52A3 p.Pro346= (c.1038T>G) pathogenic?

SLC52A3 p.Pro346= (c.1038T>G) is classified Likely benign in SLC52A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-25). Absent from gnomAD v4.1; Associated with Brown-Vialetto-van Laere syndrome 1.

What condition is associated with SLC52A3 p.Pro346= (c.1038T>G)?

SLC52A3 p.Pro346= (c.1038T>G) is associated with Brown-Vialetto-van Laere syndrome 1 (ClinVar).

How common is SLC52A3 p.Pro346= (c.1038T>G) in the general population?

SLC52A3 p.Pro346= (c.1038T>G) is absent from gnomAD v4.1 (gnomAD).

SLC52A3 p.Pro346=

c.1038T>G · rs753106817 · VCV2093041

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Brown-Vialetto-van Laere syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -4
Overall
CADD	0.612	PHRED · no single calibrated threshold — expert panels disagree

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: SLC52A3
Protein: p.Pro346=
Coding: c.1038T>G
MANE Select: NM_033409
dbSNP: rs753106817
Type: single nucleotide variant
Location: chr20:763533 (GRCh38)
Gene constraint: LOEUF 1.012 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.60 · 1 PDB
Residue 346: an α-helix

Full SLC52A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Brown-Vialetto-van Laere syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SLC52A3 p.Pro346Arg Uncertain significance ★ ⚠ same residue
SLC52A3 p.Ala312Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
SLC52A3 p.Gln259Ter Pathogenic ★★ same condition
SLC52A3 p.Glu184Ter Pathogenic ★★ same condition
SLC52A3 p.Tyr213Ter Pathogenic ★★ same condition
SLC52A3 p.Ala107Thr Uncertain significance ★★ ⚠ same condition
SLC52A3 p.Ala107Val Uncertain significance ★★ ⚠ same condition
SLC52A3 p.Ala216Thr 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/slc52a3-p-pro346 (accessed [today's date]).

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