Is SLC19A3 p.Ala183= (c.549T>C) pathogenic?

SLC19A3 p.Ala183= (c.549T>C) is classified Benign in SLC19A3 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 14.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with biotin-responsive basal ganglia disease.

What condition is associated with SLC19A3 p.Ala183= (c.549T>C)?

SLC19A3 p.Ala183= (c.549T>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 p.Ala183=

Q: How common is SLC19A3 p.Ala183= (c.549T>C) in the general population?

SLC19A3 p.Ala183= (c.549T>C) is common (popmax 14.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.549T>C · rs74693100 · VCV130325

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 14.4%, afr) — 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 1.3	GERP -3.5, phastCons 1
Overall
CADD	4.195	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.4% African / African-American · 10,782/74,998 alleles

Filtering AF 14.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.1%

Overall 0.761% 12,276/1,614,154 alleles · common exomes 6,010/1,461,888 · genomes 6,266/152,266 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14.4%	7
Remaining individualsnot grpmax-eligible	1.1%	91
Admixed American	0.955%	105
Middle Eastern	0.528%	189
South Asian	0.0264%	3,795
European (non-Finnish)	0.0148%	6,743
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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.Ala183=
Coding: c.549T>C
MANE Select: NM_025243
dbSNP: rs74693100
Type: single nucleotide variant
Location: chr2:227699166 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.96 · 19 PDB
Residue 183: 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.Ala183Val Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-ala183 (accessed [today's date]).

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