Is SLC19A2 p.Pro242fs (c.725del) pathogenic?

SLC19A2 p.Pro242fs (c.725del) is classified Pathogenic in SLC19A2 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-09-19). Ultra-rare (popmax 0.0165%, mid); Associated with thiamine-responsive megaloblastic anemia syndrome.

What condition is associated with SLC19A2 p.Pro242fs (c.725del)?

SLC19A2 p.Pro242fs (c.725del) is associated with thiamine-responsive megaloblastic anemia syndrome (ClinVar).

How common is SLC19A2 p.Pro242fs (c.725del) in the general population?

SLC19A2 p.Pro242fs (c.725del) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

SLC19A2 p.Pro242fs

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

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

c.725del · rs1571537544 · VCV5956

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 2 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.22	GERP -2.6, phastCons 0.3

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,050 alleles

Overall 6.2e-05% 1/1,614,160 alleles · ultra-rare exomes 1/1,461,848 · genomes 0/152,312 · 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.Pro242fs
Coding: c.725del
MANE Select: NM_006996
dbSNP: rs1571537544
Type: Deletion
Location: chr1:169477237 (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

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.Pro242= Likely benign ★ same residue
SLC19A2 p.Ile145fs Pathogenic same condition
SLC19A2 p.Leu195fs Pathogenic same condition
SLC19A2 p.Leu296fs Pathogenic same condition
SLC19A2 p.Thr22fs 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-pro242fs (accessed [today's date]).

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