Is SLC52A2 p.Pro73Ser (c.217C>T) pathogenic?

SLC52A2 p.Pro73Ser (c.217C>T) is classified Uncertain significance in SLC52A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-24). AlphaMissense: likely benign (0.094); Rare (popmax 0.102%, eas); Associated with Brown-Vialetto-van Laere syndrome 2.

What condition is associated with SLC52A2 p.Pro73Ser (c.217C>T)?

SLC52A2 p.Pro73Ser (c.217C>T) is associated with Brown-Vialetto-van Laere syndrome 2 (ClinVar).

How common is SLC52A2 p.Pro73Ser (c.217C>T) in the general population?

SLC52A2 p.Pro73Ser (c.217C>T) is rare (popmax 0.102%, eas) (gnomAD).

What do computational predictors say about SLC52A2 p.Pro73Ser (c.217C>T)?

AlphaMissense predicts likely benign (score 0.094) — an in-silico prediction, not a clinical call.

SLC52A2 p.Pro73Ser

c.217C>T · rs782022070 · VCV642607

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.094 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.102%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Brown-Vialetto-van Laere syndrome 2

Computational evidence

Protein change
AlphaMissense	0.094	likely benign
REVEL	0.371	indeterminate
SaProt	LLR -12.29	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -1.9, phastCons 0.058
Regional constraint	o/e 1.06	unconstrained · MANE · 1,718 bp · p 0.13 · regional, not allelic
Overall
CADD	22.0	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 0.102% East Asian · 46/44,884 alleles

Filtering AF 0.0789% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0706%

Overall 0.00322% 52/1,613,622 alleles · rare exomes 52/1,461,362 · genomes 0/152,260 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.102%	976
Remaining individualsnot grpmax-eligible	0.0064%	15,625
European (non-Finnish)	0.000169%	589,995

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.Pro73Ser
Coding: c.217C>T
MANE Select: NM_001363118
dbSNP: rs782022070
Type: single nucleotide variant
Location: chr8:144359709 (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.Pro73= Likely benign ★ 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
SLC52A2 p.Leu312Pro Pathogenic/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-pro73ser (accessed [today's date]).

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