Is SLC52A2 p.Pro48= (c.144C>G) pathogenic?

SLC52A2 p.Pro48= (c.144C>G) is classified Likely benign in SLC52A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-07-11). Absent from gnomAD v4.1; Associated with Brown-Vialetto-van Laere syndrome 2.

What condition is associated with SLC52A2 p.Pro48= (c.144C>G)?

SLC52A2 p.Pro48= (c.144C>G) is associated with Brown-Vialetto-van Laere syndrome 2 (ClinVar).

How common is SLC52A2 p.Pro48= (c.144C>G) in the general population?

SLC52A2 p.Pro48= (c.144C>G) is absent from gnomAD v4.1 (gnomAD).

SLC52A2 p.Pro48=

c.144C>G · rs1554853841 · VCV473200

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Brown-Vialetto-van Laere syndrome 2

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 -4.7	GERP -3.9
Overall
CADD	0.941	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: SLC52A2
Protein: p.Pro48=
Coding: c.144C>G
MANE Select: NM_001363118
dbSNP: rs1554853841
Type: single nucleotide variant
Location: chr8:144359636 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 1 PDB
Residue 48: an α-helix

Full SLC52A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Brown-Vialetto-van Laere syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SLC52A2 p.Pro48Leu Uncertain significance ★★ ⚠ same residue
SLC52A2 c.131-1G>C Likely pathogenic ★★ same condition
SLC52A2 p.Ala420Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
SLC52A2 p.Cys325Gly Likely pathogenic ★★ ⚠ same condition
SLC52A2 p.Gln270Ter Pathogenic/Likely pathogenic ★★ same condition
SLC52A2 p.Gly306Arg Pathogenic ★★ same condition
SLC52A2 p.Gly306Glu Likely pathogenic ★★ same condition
SLC52A2 p.Leu312Pro Pathogenic/Likely pathogenic ★★ 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/slc52a2-p-pro48 (accessed [today's date]).

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