Is SLC19A2 p.Val423Leu (c.1267G>C) pathogenic?

SLC19A2 p.Val423Leu (c.1267G>C) is classified Uncertain significance in SLC19A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). AlphaMissense: ambiguous (0.517); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SLC19A2 p.Val423Leu (c.1267G>C)?

SLC19A2 p.Val423Leu (c.1267G>C) is associated with Inborn genetic diseases (ClinVar).

How common is SLC19A2 p.Val423Leu (c.1267G>C) in the general population?

SLC19A2 p.Val423Leu (c.1267G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SLC19A2 p.Val423Leu (c.1267G>C)?

AlphaMissense predicts ambiguous (score 0.517) — an in-silico prediction, not a clinical call.

SLC19A2 p.Val423Leu

c.1267G>C · VCV3319019

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.517 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.517	ambiguous
REVEL	0.653	pathogenic-leaning
SaProt	LLR -8.77	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.054 · 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

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: SLC19A2
Protein: p.Val423Leu
Coding: c.1267G>C
MANE Select: NM_006996
Type: single nucleotide variant
Location: chr1:169468209 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 2 PDB
Residue 423: an α-helix

Full SLC19A2 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

Similar variants

SLC19A2 p.Ala201Gly Uncertain significance ★★ ⚠ same condition
SLC19A2 p.Ala431Ser Uncertain significance ★★ ⚠ same condition
SLC19A2 p.Arg275Cys Uncertain significance ★★ ⚠ same condition
SLC19A2 p.Glu321Lys Uncertain significance ★★ same condition
SLC19A2 p.Gly184Ser Uncertain significance ★★ ⚠ same condition
SLC19A2 p.Gly235Ser Uncertain significance ★★ ⚠ same condition
SLC19A2 p.Gly362Glu Uncertain significance ★★ ⚠ same condition
SLC19A2 p.Gly447Ser Uncertain significance ★★ ⚠ 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/slc19a2-p-val423leu (accessed [today's date]).

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