Is SLC52A2 p.Pro442= (c.1326C>T) pathogenic?

SLC52A2 p.Pro442= (c.1326C>T) is classified Likely benign in SLC52A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-21). Very rare (popmax 0.0039%, nfe); Associated with Brown-Vialetto-van Laere syndrome 2.

What condition is associated with SLC52A2 p.Pro442= (c.1326C>T)?

SLC52A2 p.Pro442= (c.1326C>T) is associated with Brown-Vialetto-van Laere syndrome 2 (ClinVar).

How common is SLC52A2 p.Pro442= (c.1326C>T) in the general population?

SLC52A2 p.Pro442= (c.1326C>T) is very rare (popmax 0.0039%, nfe) (gnomAD).

SLC52A2 p.Pro442=

c.1326C>T · rs1373514526 · VCV2069513

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0039%, 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 -1.3	GERP -3.2
Overall
CADD	2.018	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0039% European (non-Finnish) · 46/1,179,636 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00267%

Overall 0.00291% 47/1,612,790 alleles · very rare exomes 46/1,460,592 · genomes 1/152,198 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0039%	25,644
Admixed American	0.00167%	59,984

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.Pro442=
Coding: c.1326C>T
MANE Select: NM_001363118
dbSNP: rs1373514526
Type: single nucleotide variant
Location: chr8:144361003 (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.Pro442His Uncertain significance ★ ⚠ same residue
SLC52A2 p.Pro442Ser 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

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-pro442 (accessed [today's date]).

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