Is SLC52A3 p.Phe91Cys (c.272T>G) pathogenic?

SLC52A3 p.Phe91Cys (c.272T>G) is classified Uncertain significance in SLC52A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.3064); Very rare (popmax 0.00269%, afr); Associated with Brown-Vialetto-van Laere syndrome 1.

What condition is associated with SLC52A3 p.Phe91Cys (c.272T>G)?

SLC52A3 p.Phe91Cys (c.272T>G) is associated with Brown-Vialetto-van Laere syndrome 1 (ClinVar).

How common is SLC52A3 p.Phe91Cys (c.272T>G) in the general population?

SLC52A3 p.Phe91Cys (c.272T>G) is very rare (popmax 0.00269%, afr) (gnomAD).

What do computational predictors say about SLC52A3 p.Phe91Cys (c.272T>G)?

AlphaMissense predicts likely benign (score 0.3064) — an in-silico prediction, not a clinical call.

SLC52A3 p.Phe91Cys

c.272T>G · rs1481097414 · VCV569011

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3064 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Brown-Vialetto-van Laere syndrome 1

Computational evidence

Protein change
AlphaMissense	0.3064	likely benign
REVEL	0.9	moderately pathogenic-leaning
SaProt	LLR -10.84	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 3,966 bp · p 9.6e-06 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00269% African / African-American · 2/74,294 alleles

Filtering AF 0.000447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.00063% 10/1,586,574 alleles · very rare exomes 9/1,434,510 · genomes 1/152,064 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00269%	37,147
Finnishnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.0006%	166,633

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.Phe91Cys
Coding: c.272T>G
MANE Select: NM_033409
dbSNP: rs1481097414
Type: single nucleotide variant
Location: chr20:765503 (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 91: 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-phe91cys (accessed [today's date]).

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