Is SLC52A3 p.Pro152= (c.456C>T) pathogenic?

SLC52A3 p.Pro152= (c.456C>T) is classified Benign in SLC52A3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 21.3%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Brown-Vialetto-van Laere syndrome 1.

What condition is associated with SLC52A3 p.Pro152= (c.456C>T)?

SLC52A3 p.Pro152= (c.456C>T) is associated with Brown-Vialetto-van Laere syndrome 1 (ClinVar).

SLC52A3 p.Pro152=

Q: How common is SLC52A3 p.Pro152= (c.456C>T) in the general population?

SLC52A3 p.Pro152= (c.456C>T) is common (popmax 21.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.456C>T · rs3746807 · VCV262234

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 21.3%, eas) — too common for a highly-penetrant pathogenic allele

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 -3	GERP -4.2
Overall
CADD	5.259	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 21.3% East Asian · 9,542/44,852 alleles

Filtering AF 20.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.8%

Overall 10.5% 169,809/1,613,980 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	21.3%	5
Amishnot grpmax-eligible	12.9%	8
European (non-Finnish)	10.8%	9
Finnishnot grpmax-eligible	10.7%	9
African / African-American	10.3%	10
Remaining individualsnot grpmax-eligible	9.92%	10
South Asian	6.45%	16
Admixed American	6.35%	16
Ashkenazi Jewishnot grpmax-eligible	5.55%	18
Middle Eastern	4.92%	20

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: SLC52A3
Protein: p.Pro152=
Coding: c.456C>T
MANE Select: NM_033409
dbSNP: rs3746807
Type: single nucleotide variant
Location: chr20:765319 (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 152: 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.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
SLC52A3 p.Ala293Asp 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-pro152 (accessed [today's date]).

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