Is SLC52A2 p.Pro183= (c.549C>T) pathogenic?

SLC52A2 p.Pro183= (c.549C>T) is classified Likely benign in SLC52A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-28). Very rare (popmax 0.000339%, nfe); Associated with Brown-Vialetto-van Laere syndrome 2.

What condition is associated with SLC52A2 p.Pro183= (c.549C>T)?

SLC52A2 p.Pro183= (c.549C>T) is associated with Brown-Vialetto-van Laere syndrome 2 (ClinVar).

How common is SLC52A2 p.Pro183= (c.549C>T) in the general population?

SLC52A2 p.Pro183= (c.549C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

SLC52A2 p.Pro183=

c.549C>T · rs2489042302 · VCV2910334

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

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 -3.5	GERP -2.9
Overall
CADD	0.907	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,028 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,612,960 alleles · very rare exomes 5/1,460,624 · genomes 0/152,336 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)grpmax	0.000339%	295,007

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SLC52A2
Protein: p.Pro183=
Coding: c.549C>T
MANE Select: NM_001363118
dbSNP: rs2489042302
Type: single nucleotide variant
Location: chr8:144360041 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 1 PDB

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.Pro183Ala 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-pro183 (accessed [today's date]).

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