Is SLC19A3 p.Glu54Ter (c.160G>T) pathogenic?

SLC19A3 p.Glu54Ter (c.160G>T) is classified Pathogenic in SLC19A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). Absent from gnomAD v4.1; Associated with biotin-responsive basal ganglia disease.

What condition is associated with SLC19A3 p.Glu54Ter (c.160G>T)?

SLC19A3 p.Glu54Ter (c.160G>T) is associated with biotin-responsive basal ganglia disease (ClinVar).

How common is SLC19A3 p.Glu54Ter (c.160G>T) in the general population?

SLC19A3 p.Glu54Ter (c.160G>T) is absent from gnomAD v4.1 (gnomAD).

How is Thiamine-responsive encephalopathy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SLC19A3 p.Glu54Ter

c.160G>T · rs1695594361 · VCV2022485

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

biotin-responsive basal ganglia disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.50	loss · gain 0.05 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 2.4	GERP -0.22, phastCons 0.99
Overall
CADD	49.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SLC19A3
Protein: p.Glu54Ter
Coding: c.160G>T
MANE Select: NM_025243
dbSNP: rs1695594361
Type: single nucleotide variant
Location: chr2:227699555 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.96 · 19 PDB
Residue 54: an α-helix

Full SLC19A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

biotin-responsive basal ganglia disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Thiamine-responsive encephalopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent

Similar variants

SLC19A3 c.1172+1G>A Pathogenic/Likely pathogenic ★★ same condition
SLC19A3 c.1172+2T>G Pathogenic ★★ same condition
SLC19A3 c.1173-1G>A Pathogenic/Likely pathogenic ★★ same condition
SLC19A3 c.151-1G>C Likely pathogenic ★★ same condition
SLC19A3 c.980-14A>G Pathogenic/Likely pathogenic ★★ same condition
SLC19A3 p.Gly23Val Pathogenic/Likely pathogenic ★★ same condition
SLC19A3 p.Met1Leu Likely pathogenic ★★ same condition
SLC19A3 p.Ser181Pro 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/slc19a3-p-glu54ter (accessed [today's date]).

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