Is SLC19A2 p.Phe129Leu (c.387T>G) pathogenic?

SLC19A2 p.Phe129Leu (c.387T>G) is classified Uncertain significance in SLC19A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). AlphaMissense: likely pathogenic (0.7156); Absent from gnomAD v4.1; Associated with thiamine-responsive megaloblastic anemia syndrome.

What condition is associated with SLC19A2 p.Phe129Leu (c.387T>G)?

SLC19A2 p.Phe129Leu (c.387T>G) is associated with thiamine-responsive megaloblastic anemia syndrome (ClinVar).

How common is SLC19A2 p.Phe129Leu (c.387T>G) in the general population?

SLC19A2 p.Phe129Leu (c.387T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SLC19A2 p.Phe129Leu (c.387T>G)?

AlphaMissense predicts likely pathogenic (score 0.7156) — an in-silico prediction, not a clinical call.

SLC19A2 p.Phe129Leu

Q: How is Thiamine-responsive megaloblastic anemia syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.387T>G · VCV3600091

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7156 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

thiamine-responsive megaloblastic anemia syndrome

Computational evidence

Protein change
AlphaMissense	0.7156	likely pathogenic
REVEL	0.625	indeterminate
SaProt	LLR -8.89	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 1.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.054 · regional, not allelic
Overall
CADD	22.3	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.Phe129Leu
Coding: c.387T>G
MANE Select: NM_006996
Type: single nucleotide variant
Location: chr1:169477575 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 2 PDB
Residue 129: an α-helix

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

Disease context

thiamine-responsive megaloblastic anemia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Thiamine-responsive megaloblastic anemia syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

SLC19A2 c.1223+1G>A Pathogenic ★★ same condition
SLC19A2 c.807+2T>G Likely pathogenic ★★ same condition
SLC19A2 p.Arg162Ter Pathogenic ★★ same condition
SLC19A2 p.Arg397Ter Pathogenic/Likely pathogenic ★★ same condition
SLC19A2 p.Gln233Ter Pathogenic ★★ same condition
SLC19A2 p.Gly105Glu Pathogenic/Likely pathogenic ★★ same condition
SLC19A2 p.Gly172Asp Pathogenic/Likely pathogenic ★★ same condition
SLC19A2 p.Gly334Asp 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/slc19a2-p-phe129leu (accessed [today's date]).

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