Is SLC52A3 p.Pro35= (c.105C>T) pathogenic?

SLC52A3 p.Pro35= (c.105C>T) is classified Likely benign in SLC52A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-19). Ultra-rare (popmax 0.0112%, eas); Associated with Brown-Vialetto-van Laere syndrome 1.

What condition is associated with SLC52A3 p.Pro35= (c.105C>T)?

SLC52A3 p.Pro35= (c.105C>T) is associated with Brown-Vialetto-van Laere syndrome 1 (ClinVar).

How common is SLC52A3 p.Pro35= (c.105C>T) in the general population?

SLC52A3 p.Pro35= (c.105C>T) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

SLC52A3 p.Pro35=

c.105C>T · rs376995195 · VCV1597047

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

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 -9.9	GERP -3.9
Overall
CADD	3.265	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% East Asian · 5/44,842 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000992% 16/1,612,780 alleles · ultra-rare exomes 14/1,461,100 · genomes 2/151,680 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0112%	8,968
Remaining individualsnot grpmax-eligible	0.0032%	31,232
African / African-American	0.00134%	74,718
South Asian	0.0011%	90,738
European (non-Finnish)	0.000593%	168,527

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.Pro35=
Coding: c.105C>T
MANE Select: NM_033409
dbSNP: rs376995195
Type: single nucleotide variant
Location: chr20:765670 (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 35: a β-strand

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-pro35 (accessed [today's date]).

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