Is SLC19A3 p.Glu120= (c.360G>A) pathogenic?

SLC19A3 p.Glu120= (c.360G>A) is classified Conflicting classifications of pathogenicity in SLC19A3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-28). Rare (popmax 0.238%, sas); Associated with biotin-responsive basal ganglia disease.

What condition is associated with SLC19A3 p.Glu120= (c.360G>A)?

SLC19A3 p.Glu120= (c.360G>A) is associated with biotin-responsive basal ganglia disease (ClinVar).

How common is SLC19A3 p.Glu120= (c.360G>A) in the general population?

SLC19A3 p.Glu120= (c.360G>A) is rare (popmax 0.238%, sas) (gnomAD).

How is Thiamine-responsive encephalopathy inherited?

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

SLC19A3 p.Glu120=

c.360G>A · rs566837952 · VCV897180

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.238%, sas)

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 1.8	GERP 1.9, phastCons 1
Overall
CADD	9.282	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.238% South Asian · 217/91,092 alleles

Filtering AF 0.212% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.202%

Overall 0.0142% 230/1,614,186 alleles · rare exomes 219/1,461,892 · genomes 11/152,294 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.238%	420
Remaining individualsnot grpmax-eligible	0.0176%	5,683
European (non-Finnish)	0.000169%	590,019

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.Glu120=
Coding: c.360G>A
MANE Select: NM_025243
dbSNP: rs566837952
Type: single nucleotide variant
Location: chr2:227699355 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.96 · 19 PDB
Residue 120: 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.Glu120Lys 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-glu120 (accessed [today's date]).

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