Is SLC19A3 c.*348A>C pathogenic?

SLC19A3 c.348A>C is classified Likely benign in SLC19A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Low-frequency (popmax 1.14%, afr); Associated with biotin-responsive basal ganglia disease.

What condition is associated with SLC19A3 c.*348A>C?

SLC19A3 c.*348A>C is associated with biotin-responsive basal ganglia disease (ClinVar).

How common is SLC19A3 c.*348A>C in the general population?

SLC19A3 c.*348A>C is low-frequency (popmax 1.14%, afr) (gnomAD).

How is Thiamine-responsive encephalopathy inherited?

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

SLC19A3 c.*348A>C

rs112957132 · VCV334869

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.14%, afr)

Conditions

biotin-responsive basal ganglia disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.092	GERP -2.7
Non-coding constraint	Z 0.87	1 kb window · o/e 0.94 · regional · uncalibrated
Overall
CADD	2.596	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.14% African / African-American · 489/42,948 alleles

Filtering AF 1.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.02%

Overall 0.268% 539/201,124 alleles · low-frequency exomes 20/48,870 · genomes 519/152,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.14%	88
Middle Eastern	0.427%	234
Remaining individualsnot grpmax-eligible	0.266%	376
Admixed American	0.145%	691
South Asian	0.0111%	9,012
European (non-Finnish)	0.00711%	14,070

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
Coding: c.*348A>C
MANE Select: NM_025243
dbSNP: rs112957132
Type: single nucleotide variant
Location: chr2:227687049 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.96 · 19 PDB

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-c-star-348a-c (accessed [today's date]).

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