Is SLC52A2 p.Ser52Phe (c.155C>T) pathogenic?

SLC52A2 p.Ser52Phe (c.155C>T) is classified Pathogenic in SLC52A2 (ClinVar, Single submitter, 3 submitters; last evaluated 2025-09-16). AlphaMissense: ambiguous (0.5444); Very rare (popmax 0.00212%, nfe); Associated with Brown-Vialetto-van Laere syndrome 2.

What condition is associated with SLC52A2 p.Ser52Phe (c.155C>T)?

SLC52A2 p.Ser52Phe (c.155C>T) is associated with Brown-Vialetto-van Laere syndrome 2 (ClinVar).

How common is SLC52A2 p.Ser52Phe (c.155C>T) in the general population?

SLC52A2 p.Ser52Phe (c.155C>T) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about SLC52A2 p.Ser52Phe (c.155C>T)?

AlphaMissense predicts ambiguous (score 0.5444) — an in-silico prediction, not a clinical call.

SLC52A2 p.Ser52Phe

c.155C>T · rs397514657 · VCV40231

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5444 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Conditions

Brown-Vialetto-van Laere syndrome 2

Computational evidence

Protein change
AlphaMissense	0.5444	ambiguous
REVEL	0.534	indeterminate
SaProt	LLR -12.23	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,718 bp · p 0.13 · regional, not allelic
Overall
CADD	24.0	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 0.00212% European (non-Finnish) · 25/1,179,928 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00167% 27/1,613,764 alleles · very rare exomes 25/1,461,544 · genomes 2/152,220 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,197
Admixed American	0.00167%	59,988
African / African-American	0.00133%	74,940

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.Ser52Phe
Coding: c.155C>T
MANE Select: NM_001363118
dbSNP: rs397514657
Type: single nucleotide variant
Location: chr8:144359647 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 1 PDB
Residue 52: a UniProt-annotated variant site (in bvvls2; decreased riboflavin transport); an α-helix

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.Ser52Thr Likely benign ★ same residue
SLC52A2 p.Ser52Pro Likely pathogenic ★ 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-ser52phe (accessed [today's date]).

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