Is SLC19A3 c.*1815A>C pathogenic?

SLC19A3 c.1815A>C is classified Benign in SLC19A3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-13). Common (popmax 46%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with biotin-responsive basal ganglia disease.

What condition is associated with SLC19A3 c.*1815A>C?

SLC19A3 c.*1815A>C is associated with biotin-responsive basal ganglia disease (ClinVar).

How is Thiamine-responsive encephalopathy inherited?

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

SLC19A3 c.*1815A>C

Q: How common is SLC19A3 c.*1815A>C in the general population?

SLC19A3 c.*1815A>C is common (popmax 46%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs34020562 · VCV334844

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 46%, nfe) — too common for a highly-penetrant pathogenic allele

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.71	GERP 0.21, phastCons 0.001
Non-coding constraint	Z 0.58	1 kb window · o/e 0.95 · regional · uncalibrated
Overall
CADD	2.339	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 46% European (non-Finnish) · 31,250/67,960 alleles

Filtering AF 45.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 45.4%

Overall 37.7% 57,232/151,982 alleles · common exomes 1/8 · genomes 57,231/151,974 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	46%	2
Finnishnot grpmax-eligible	44.3%	2
Middle Eastern	43.2%	2
Amishnot grpmax-eligible	40.9%	2
Ashkenazi Jewishnot grpmax-eligible	38.4%	3
Remaining individualsnot grpmax-eligible	37.4%	3
African / African-American	31%	3
Admixed American	30.3%	3
South Asian	25%	4
East Asian	0.407%	246

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.*1815A>C
MANE Select: NM_025243
dbSNP: rs34020562
Type: single nucleotide variant
Location: chr2:227685582 (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-1815a-c (accessed [today's date]).

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