Is SLC19A2 p.Ile354del (c.1061_1063del) pathogenic?

SLC19A2 p.Ile354del (c.10611063del) is classified Uncertain significance in SLC19A2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-10). Ultra-rare (popmax 0.0825%, mid); Associated with Inborn genetic diseases.

What condition is associated with SLC19A2 p.Ile354del (c.1061_1063del)?

SLC19A2 p.Ile354del (c.1061_1063del) is associated with Inborn genetic diseases, thiamine-responsive megaloblastic anemia syndrome (ClinVar).

How common is SLC19A2 p.Ile354del (c.1061_1063del) in the general population?

SLC19A2 p.Ile354del (c.1061_1063del) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

SLC19A2 p.Ile354del

c.1061_1063del · rs775393998 · VCV2348763

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP 2, phastCons 1
Overall
CADD	17.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0825% Middle Eastern · 5/6,062 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.00421% 68/1,613,946 alleles · ultra-rare exomes 61/1,461,678 · genomes 7/152,268 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
South Asian	0.0351%	2,846
Remaining individualsnot grpmax-eligible	0.008%	12,501
African / African-American	0.004%	25,001
European (non-Finnish)	0.00195%	51,300

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.Ile354del
Coding: c.1061_1063del
MANE Select: NM_006996
dbSNP: rs775393998
Type: Deletion
Location: chr1:169468804 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: thiamine-responsive megaloblastic anemia syndrome

Similar variants

SLC19A2 p.Tyr144fs Pathogenic/Likely pathogenic ★★ same condition
SLC19A2 p.Leu304fs Likely pathogenic ★ same condition
SLC19A2 p.Pro242fs Pathogenic ★ same condition
SLC19A2 p.Ile354Thr Uncertain significance ★ ⚠ 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-ile354del (accessed [today's date]).

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