Is SLC19A2 p.Leu64Pro (c.191T>C) pathogenic?

SLC19A2 p.Leu64Pro (c.191T>C) is classified Likely pathogenic in SLC19A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-02). AlphaMissense: likely pathogenic (0.9325); Very rare (popmax 0.0023%, sas).

How common is SLC19A2 p.Leu64Pro (c.191T>C) in the general population?

SLC19A2 p.Leu64Pro (c.191T>C) is very rare (popmax 0.0023%, sas) (gnomAD).

What do computational predictors say about SLC19A2 p.Leu64Pro (c.191T>C)?

AlphaMissense predicts likely pathogenic (score 0.9325) — an in-silico prediction, not a clinical call.

SLC19A2 p.Leu64Pro

c.191T>C · rs1658540031 · VCV2169485

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9325 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0023%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9325	likely pathogenic ✓ concordant with ClinVar · top 8% in SLC19A2
REVEL	0.874	moderately pathogenic-leaning
SaProt	LLR -14.65	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.054 · regional, not allelic
Overall
CADD	31.0	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 0.0023% South Asian · 2/87,126 alleles

Filtering AF 0.000381% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000143%

Overall 0.000126% 2/1,586,632 alleles · very rare exomes 2/1,434,348 · genomes 0/152,284 · 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: SLC19A2
Protein: p.Leu64Pro
Coding: c.191T>C
MANE Select: NM_006996
dbSNP: rs1658540031
Type: single nucleotide variant
Location: chr1:169485576 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 2 PDB

Full SLC19A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC19A2 c.1223+1G>A Pathogenic ★★ same type
SLC19A2 c.807+2T>G Likely pathogenic ★★ same type
SLC19A2 p.Arg162Ter Pathogenic ★★ same type
SLC19A2 p.Arg397Ter Pathogenic/Likely pathogenic ★★ same type
SLC19A2 p.Gln233Ter Pathogenic ★★ same type
SLC19A2 p.Glu66Ter Pathogenic ★★ same type
SLC19A2 p.Gly105Glu Pathogenic/Likely pathogenic ★★ same type
SLC19A2 p.Gly172Asp Pathogenic/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/slc19a2-p-leu64pro (accessed [today's date]).

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