Is SLC19A3 p.Ile51Val (c.151A>G) pathogenic?

SLC19A3 p.Ile51Val (c.151A>G) is classified Uncertain significance in SLC19A3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-18). AlphaMissense: likely benign (0.0941); Very rare (popmax 0.00878%, sas); Associated with biotin-responsive basal ganglia disease.

What condition is associated with SLC19A3 p.Ile51Val (c.151A>G)?

SLC19A3 p.Ile51Val (c.151A>G) is associated with biotin-responsive basal ganglia disease (ClinVar).

How common is SLC19A3 p.Ile51Val (c.151A>G) in the general population?

SLC19A3 p.Ile51Val (c.151A>G) is very rare (popmax 0.00878%, sas) (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.Ile51Val (c.151A>G)?

AlphaMissense predicts likely benign (score 0.0941) — an in-silico prediction, not a clinical call.

SLC19A3 p.Ile51Val

c.151A>G · rs764398318 · VCV533545

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0941 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

biotin-responsive basal ganglia disease

Computational evidence

Protein change
AlphaMissense	0.0941	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -4.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.79	GERP 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 15 kb · p 0.85 · regional, not allelic
Overall
CADD	0.398	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00878% South Asian · 8/91,088 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00167% 27/1,613,846 alleles · very rare exomes 26/1,461,616 · genomes 1/152,230 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,386
Remaining individualsnot grpmax-eligible	0.0064%	15,619
African / African-American	0.00133%	74,938
European (non-Finnish)	0.00119%	84,277

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.Ile51Val
Coding: c.151A>G
MANE Select: NM_025243
dbSNP: rs764398318
Type: single nucleotide variant
Location: chr2:227699564 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.96 · 19 PDB
Residue 51: 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.Ile51Met 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-ile51val (accessed [today's date]).

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