Is SLC52A3 p.Phe76= (c.228C>T) pathogenic?

SLC52A3 p.Phe76= (c.228C>T) is classified Likely benign in SLC52A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-19). Very rare (popmax 0.00231%, sas); Associated with Brown-Vialetto-van Laere syndrome 1.

What condition is associated with SLC52A3 p.Phe76= (c.228C>T)?

SLC52A3 p.Phe76= (c.228C>T) is associated with Brown-Vialetto-van Laere syndrome 1 (ClinVar).

How common is SLC52A3 p.Phe76= (c.228C>T) in the general population?

SLC52A3 p.Phe76= (c.228C>T) is very rare (popmax 0.00231%, sas) (gnomAD).

SLC52A3 p.Phe76=

c.228C>T · rs1599959406 · VCV757928

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00231%, sas)

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 0.024	GERP -2.4
Overall
CADD	3.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00231% South Asian · 2/86,426 alleles

Filtering AF 0.000384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000144%

Overall 0.00014% 2/1,424,986 alleles · very rare

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.Phe76=
Coding: c.228C>T
MANE Select: NM_033409
dbSNP: rs1599959406
Type: single nucleotide variant
Location: chr20:765547 (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 76: 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-phe76 (accessed [today's date]).

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