Is SLC19A2 p.Tyr81Ter (c.242dup) pathogenic?

SLC19A2 p.Tyr81Ter (c.242dup) is classified Pathogenic in SLC19A2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-27). Very rare (popmax 0.00439%, sas); Associated with SLC19A2-related disorder.

What condition is associated with SLC19A2 p.Tyr81Ter (c.242dup)?

SLC19A2 p.Tyr81Ter (c.242dup) is associated with SLC19A2-related disorder, thiamine-responsive megaloblastic anemia syndrome (ClinVar).

How common is SLC19A2 p.Tyr81Ter (c.242dup) in the general population?

SLC19A2 p.Tyr81Ter (c.242dup) is very rare (popmax 0.00439%, sas) (gnomAD).

SLC19A2 p.Tyr81Ter

c.242dup · rs752104654 · VCV5961

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

SLC19A2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	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 1.7	GERP 0.45, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,016 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000434% 7/1,611,552 alleles · very rare exomes 7/1,460,012 · genomes 0/151,540 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,754
Remaining individualsnot grpmax-eligible	0.0016%	62,394
European (non-Finnish)	0.00017%	589,324

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.Tyr81Ter
Coding: c.242dup
MANE Select: NM_006996
dbSNP: rs752104654
Type: Duplication
Location: chr1:169477719 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 2 PDB
Residue 81: an α-helix

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

Disease context

SLC19A2-related disorder

Also linked: thiamine-responsive megaloblastic anemia syndrome

Similar variants

SLC19A2 p.Glu254Ter Pathogenic ★★ same condition
SLC19A2 p.Ala136fs Pathogenic ★ same condition
SLC19A2 p.Arg67fs Likely pathogenic ★ same condition
SLC19A2 c.1224-4dup Conflicting classifications of pathogenicity ★ same condition
SLC19A2 p.Met479fs Uncertain significance ★ same condition
SLC19A2 p.Thr495fs Uncertain significance ★ same condition
SLC19A2 p.Tyr81= Likely benign ★ same residue
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-tyr81ter (accessed [today's date]).

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