Is SLC19A3 p.Leu161fs (c.482_483del) pathogenic?

SLC19A3 p.Leu161fs (c.482483del) is classified Pathogenic/Likely pathogenic in SLC19A3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-02-20). Ultra-rare (popmax 0.011%, sas); Associated with biotin-responsive basal ganglia disease.

What condition is associated with SLC19A3 p.Leu161fs (c.482_483del)?

SLC19A3 p.Leu161fs (c.482_483del) is associated with biotin-responsive basal ganglia disease (ClinVar).

How common is SLC19A3 p.Leu161fs (c.482_483del) in the general population?

SLC19A3 p.Leu161fs (c.482_483del) is ultra-rare (popmax 0.011%, sas) (gnomAD).

How is Thiamine-responsive encephalopathy inherited?

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

SLC19A3 p.Leu161fs

c.482_483del · rs1271884981 · VCV973536

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Conditions

biotin-responsive basal ganglia disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,080 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00062% 10/1,614,114 alleles · ultra-rare exomes 10/1,461,830 · genomes 0/152,284 · joint denominator

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: SLC19A3
Protein: p.Leu161fs
Coding: c.482_483del
MANE Select: NM_025243
dbSNP: rs1271884981
Type: Deletion
Location: chr2:227699232 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.96 · 19 PDB
Residue 161: 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 p.Leu161= Conflicting classifications of pathogenicity ★ same residue
SLC19A3 p.Leu161Ser Uncertain significance ★ ⚠ same residue
SLC19A3 p.His200fs Pathogenic ★★ same condition
SLC19A3 p.Lys208fs Pathogenic/Likely pathogenic ★★ same condition
SLC19A3 p.Tyr38fs Pathogenic/Likely pathogenic ★★ same condition
SLC19A3 p.Val299fs Pathogenic ★★ same condition
SLC19A3 p.Val58fs Pathogenic ★★ same condition
SLC19A3 c.980-4del Benign ★★ 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-leu161fs (accessed [today's date]).

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