Is SLC19A3 p.Val109Ile (c.325G>A) pathogenic?

SLC19A3 p.Val109Ile (c.325G>A) is classified Conflicting classifications of pathogenicity in SLC19A3 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-21). AlphaMissense: likely benign (0.1197); Rare (popmax 0.33%, mid); Associated with Inborn genetic diseases.

What condition is associated with SLC19A3 p.Val109Ile (c.325G>A)?

SLC19A3 p.Val109Ile (c.325G>A) is associated with Inborn genetic diseases, biotin-responsive basal ganglia disease (ClinVar).

How common is SLC19A3 p.Val109Ile (c.325G>A) in the general population?

SLC19A3 p.Val109Ile (c.325G>A) is rare (popmax 0.33%, mid) (gnomAD).

What do computational predictors say about SLC19A3 p.Val109Ile (c.325G>A)?

AlphaMissense predicts likely benign (score 0.1197) — an in-silico prediction, not a clinical call.

SLC19A3 p.Val109Ile

c.325G>A · rs780569649 · VCV285907

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1197 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.33%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1197	likely benign
REVEL	0.216	benign-leaning
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.13	GERP -2, phastCons 0.004
Regional constraint	o/e 0.99	unconstrained · MANE · 15 kb · p 0.85 · regional, not allelic
Overall
CADD	14.01	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 0.33% Middle Eastern · 20/6,062 alleles

Filtering AF 0.219% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.183%

Overall 0.00812% 131/1,614,178 alleles · rare exomes 116/1,461,892 · genomes 15/152,286 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.33%	303
African / African-American	0.0147%	6,823
Remaining individualsnot grpmax-eligible	0.0144%	6,945
Admixed American	0.0117%	8,573
South Asian	0.00878%	11,384
European (non-Finnish)	0.00644%	15,527

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.Val109Ile
Coding: c.325G>A
MANE Select: NM_025243
dbSNP: rs780569649
Type: single nucleotide variant
Location: chr2:227699390 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.96 · 19 PDB
Residue 109: an α-helix

Full SLC19A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: biotin-responsive basal ganglia disease

Similar variants

SLC19A3 p.Val109= Likely benign ★ same residue
SLC19A3 p.Val109Ala 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

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-val109ile (accessed [today's date]).

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