Is SLC19A3 p.Lys468fs (c.1403del) pathogenic?

SLC19A3 p.Lys468fs (c.1403del) is classified Likely pathogenic in SLC19A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). Very rare (popmax 0.000169%, nfe); Associated with biotin-responsive basal ganglia disease.

What condition is associated with SLC19A3 p.Lys468fs (c.1403del)?

SLC19A3 p.Lys468fs (c.1403del) is associated with biotin-responsive basal ganglia disease (ClinVar).

How common is SLC19A3 p.Lys468fs (c.1403del) in the general population?

SLC19A3 p.Lys468fs (c.1403del) is very rare (popmax 0.000169%, nfe) (gnomAD).

How is Thiamine-responsive encephalopathy inherited?

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

SLC19A3 p.Lys468fs

c.1403del · rs2470552983 · VCV2732790

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

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	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.44	GERP -1.5

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,004 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,130 alleles · very rare exomes 2/1,461,816 · genomes 0/152,314 · 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.Lys468fs
Coding: c.1403del
MANE Select: NM_025243
dbSNP: rs2470552983
Type: Deletion
Location: chr2:227687485 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.96 · 19 PDB
Residue 468: the 'disordered' region

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.His200fs Pathogenic ★★ same condition
SLC19A3 p.Leu161fs Pathogenic/Likely 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
SLC19A3 p.Ala286fs 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-lys468fs (accessed [today's date]).

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