Is SLC19A3 p.Tyr38Cys (c.113A>G) pathogenic?

SLC19A3 p.Tyr38Cys (c.113A>G) is classified Uncertain significance in SLC19A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-14). AlphaMissense: ambiguous (0.4992); Very rare (popmax 0.000254%, nfe).

How common is SLC19A3 p.Tyr38Cys (c.113A>G) in the general population?

SLC19A3 p.Tyr38Cys (c.113A>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about SLC19A3 p.Tyr38Cys (c.113A>G)?

AlphaMissense predicts ambiguous (score 0.4992) — an in-silico prediction, not a clinical call.

SLC19A3 p.Tyr38Cys

c.113A>G · rs766975844 · VCV1313272

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4992 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4992	ambiguous
REVEL	0.777	moderately pathogenic-leaning
SaProt	LLR -14.58	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.5	GERP 0.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 15 kb · p 0.85 · regional, not allelic
Overall
CADD	26.1	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 0.000254% European (non-Finnish) · 3/1,179,712 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,726 alleles · very rare exomes 3/1,461,536 · genomes 0/152,190 · joint denominator

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.Tyr38Cys
Coding: c.113A>G
MANE Select: NM_025243
dbSNP: rs766975844
Type: single nucleotide variant
Location: chr2:227702206 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.96 · 19 PDB
Residue 38: an α-helix

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

Similar variants

SLC19A3 p.Tyr38fs Pathogenic/Likely pathogenic ★★ same residue
SLC19A3 c.1172+1G>A Pathogenic/Likely pathogenic ★★ same type
SLC19A3 c.1172+2T>G Pathogenic ★★ same type
SLC19A3 c.1173-1G>A Pathogenic/Likely pathogenic ★★ same type
SLC19A3 c.151-1G>C Likely pathogenic ★★ same type
SLC19A3 c.980-14A>G Pathogenic/Likely pathogenic ★★ same type
SLC19A3 p.Gly23Val Pathogenic/Likely pathogenic ★★ same type
SLC19A3 p.Met1Leu Likely pathogenic ★★ same type

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-tyr38cys (accessed [today's date]).

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