Is SLC19A2 p.Leu116Phe (c.346C>T) pathogenic?

SLC19A2 p.Leu116Phe (c.346C>T) is classified Uncertain significance in SLC19A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). AlphaMissense: ambiguous (0.5092); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SLC19A2 p.Leu116Phe (c.346C>T)?

SLC19A2 p.Leu116Phe (c.346C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SLC19A2 p.Leu116Phe (c.346C>T) in the general population?

SLC19A2 p.Leu116Phe (c.346C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SLC19A2 p.Leu116Phe (c.346C>T)?

AlphaMissense predicts ambiguous (score 0.5092) — an in-silico prediction, not a clinical call.

SLC19A2 p.Leu116Phe

c.346C>T · VCV3319017

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5092 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5092	ambiguous
REVEL	0.595	indeterminate
SaProt	LLR -11.27	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 0.43, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.054 · regional, not allelic
Overall
CADD	27.0	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

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.Leu116Phe
Coding: c.346C>T
MANE Select: NM_006996
Type: single nucleotide variant
Location: chr1:169477616 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 2 PDB
Residue 116: 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-leu116phe (accessed [today's date]).

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