Is SLC19A2 p.Leu296fs (c.885del) pathogenic?

SLC19A2 p.Leu296fs (c.885del) is classified Pathogenic in SLC19A2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1999-07-01). No gnomAD frequency available for this variant; Associated with thiamine-responsive megaloblastic anemia syndrome.

What condition is associated with SLC19A2 p.Leu296fs (c.885del)?

SLC19A2 p.Leu296fs (c.885del) is associated with thiamine-responsive megaloblastic anemia syndrome (ClinVar).

How common is SLC19A2 p.Leu296fs (c.885del) in the general population?

SLC19A2 p.Leu296fs (c.885del) is no gnomAD frequency available for this variant (gnomAD).

SLC19A2 p.Leu296fs

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

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

c.885del · rs1571532822 · VCV5959

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

thiamine-responsive megaloblastic anemia syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 10	GERP 2.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SLC19A2
Protein: p.Leu296fs
Coding: c.885del
MANE Select: NM_006996
dbSNP: rs1571532822
Type: Deletion
Location: chr1:169470109 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 2 PDB
Residue 296: 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 p.Tyr144fs Pathogenic/Likely pathogenic ★★ same condition
SLC19A2 p.Ile354del Uncertain significance ★★ same condition
SLC19A2 p.Leu304fs Likely pathogenic ★ same condition
SLC19A2 p.Pro242fs Pathogenic ★ same condition
SLC19A2 p.Ile145fs Pathogenic same condition
SLC19A2 p.Leu195fs Pathogenic same condition
SLC19A2 p.Thr22fs Pathogenic same condition
SLC19A2 c.1223+1G>A 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-leu296fs (accessed [today's date]).

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