Is SLC19A3 p.Ser382Asn (c.1145G>A) pathogenic?

SLC19A3 p.Ser382Asn (c.1145G>A) is classified Conflicting classifications of pathogenicity in SLC19A3 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-09-14). AlphaMissense: likely benign (0.2764); Rare (popmax 0.208%, afr); Associated with biotin-responsive basal ganglia disease.

What condition is associated with SLC19A3 p.Ser382Asn (c.1145G>A)?

SLC19A3 p.Ser382Asn (c.1145G>A) is associated with biotin-responsive basal ganglia disease (ClinVar).

How common is SLC19A3 p.Ser382Asn (c.1145G>A) in the general population?

SLC19A3 p.Ser382Asn (c.1145G>A) is rare (popmax 0.208%, afr) (gnomAD).

How is Thiamine-responsive encephalopathy inherited?

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

What do computational predictors say about SLC19A3 p.Ser382Asn (c.1145G>A)?

AlphaMissense predicts likely benign (score 0.2764) — an in-silico prediction, not a clinical call.

SLC19A3 p.Ser382Asn

c.1145G>A · rs145288025 · VCV288883

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2764 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.208%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

biotin-responsive basal ganglia disease

Computational evidence

Protein change
AlphaMissense	0.2764	likely benign
REVEL	0.475	indeterminate
SaProt	LLR -9.79	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -1.3, phastCons 0.98
Regional constraint	o/e 0.99	unconstrained · MANE · 15 kb · p 0.85 · regional, not allelic
Overall
CADD	19.09	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.208% African / African-American · 156/75,010 alleles

Filtering AF 0.181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.171%

Overall 0.0159% 256/1,614,080 alleles · rare exomes 151/1,461,866 · genomes 105/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.208%	481
Middle Eastern	0.0661%	1,512
Admixed American	0.045%	2,223
Remaining individualsnot grpmax-eligible	0.0224%	4,465
European (non-Finnish)	0.00466%	21,455

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.Ser382Asn
Coding: c.1145G>A
MANE Select: NM_025243
dbSNP: rs145288025
Type: single nucleotide variant
Location: chr2:227695916 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.96 · 19 PDB
Residue 382: 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 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-p-ser382asn (accessed [today's date]).

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