Is SLC19A3 p.Ala122= (c.366C>T) pathogenic?

SLC19A3 p.Ala122= (c.366C>T) is classified Likely benign in SLC19A3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-30). Ultra-rare (popmax 0.0201%, eas); Associated with biotin-responsive basal ganglia disease.

What condition is associated with SLC19A3 p.Ala122= (c.366C>T)?

SLC19A3 p.Ala122= (c.366C>T) is associated with biotin-responsive basal ganglia disease (ClinVar).

How common is SLC19A3 p.Ala122= (c.366C>T) in the general population?

SLC19A3 p.Ala122= (c.366C>T) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

How is Thiamine-responsive encephalopathy inherited?

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

SLC19A3 p.Ala122=

c.366C>T · rs548635197 · VCV1100652

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

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 0.86	GERP -0.097, phastCons 1
Overall
CADD	7.383	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% East Asian · 9/44,874 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00167% 27/1,614,170 alleles · ultra-rare exomes 22/1,461,890 · genomes 5/152,280 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,986
South Asian	0.00878%	11,386
African / African-American	0.00666%	15,008
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.000339%	295,010

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.Ala122=
Coding: c.366C>T
MANE Select: NM_025243
dbSNP: rs548635197
Type: single nucleotide variant
Location: chr2:227699349 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.96 · 19 PDB
Residue 122: 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.Ala122_Tyr126del Uncertain significance ★ 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-ala122 (accessed [today's date]).

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