Is SLC19A3 p.Pro30Thr (c.88C>A) pathogenic?

SLC19A3 p.Pro30Thr (c.88C>A) is classified Uncertain significance in SLC19A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-19). AlphaMissense: likely pathogenic (0.6323); Absent from gnomAD v4.1; Associated with biotin-responsive basal ganglia disease.

What condition is associated with SLC19A3 p.Pro30Thr (c.88C>A)?

SLC19A3 p.Pro30Thr (c.88C>A) is associated with biotin-responsive basal ganglia disease (ClinVar).

How common is SLC19A3 p.Pro30Thr (c.88C>A) in the general population?

SLC19A3 p.Pro30Thr (c.88C>A) is absent from gnomAD v4.1 (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.Pro30Thr (c.88C>A)?

AlphaMissense predicts likely pathogenic (score 0.6323) — an in-silico prediction, not a clinical call.

SLC19A3 p.Pro30Thr

c.88C>A · rs2106332649 · VCV1052179

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6323 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

biotin-responsive basal ganglia disease

Computational evidence

Protein change
AlphaMissense	0.6323	likely pathogenic
REVEL	0.854	moderately pathogenic-leaning
SaProt	LLR -12.76	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.92, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 15 kb · p 0.85 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SLC19A3
Protein: p.Pro30Thr
Coding: c.88C>A
MANE Select: NM_025243
dbSNP: rs2106332649
Type: single nucleotide variant
Location: chr2:227702231 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.96 · 19 PDB

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-pro30thr (accessed [today's date]).

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