Is SLC19A2 p.Thr365Ser (c.1093A>T) pathogenic?

SLC19A2 p.Thr365Ser (c.1093A>T) is classified Benign/Likely benign in SLC19A2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1174); Low-frequency (popmax 1.39%, amr); Associated with thiamine-responsive megaloblastic anemia syndrome.

What condition is associated with SLC19A2 p.Thr365Ser (c.1093A>T)?

SLC19A2 p.Thr365Ser (c.1093A>T) is associated with thiamine-responsive megaloblastic anemia syndrome (ClinVar).

How common is SLC19A2 p.Thr365Ser (c.1093A>T) in the general population?

SLC19A2 p.Thr365Ser (c.1093A>T) is low-frequency (popmax 1.39%, amr) (gnomAD).

What do computational predictors say about SLC19A2 p.Thr365Ser (c.1093A>T)?

AlphaMissense predicts likely benign (score 0.1174) — an in-silico prediction, not a clinical call.

SLC19A2 p.Thr365Ser

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

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

c.1093A>T · rs150049339 · VCV678373

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1174 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.39%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

thiamine-responsive megaloblastic anemia syndrome

Computational evidence

Protein change
AlphaMissense	0.1174	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -6.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	acceptor loss, 37 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.24	GERP -1.7
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.054 · regional, not allelic
Overall
CADD	14.16	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

Grpmax group 1.39% Admixed American · 834/59,990 alleles

Filtering AF 1.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.28%

Overall 0.0557% 899/1,613,926 alleles · low-frequency exomes 727/1,461,686 · genomes 172/152,240 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	1.39%	72
Remaining individualsnot grpmax-eligible	0.056%	1,786
African / African-American	0.0187%	5,356
European (non-Finnish)	0.00136%	73,744

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.Thr365Ser
Coding: c.1093A>T
MANE Select: NM_006996
dbSNP: rs150049339
Type: single nucleotide variant
Location: chr1:169468774 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 2 PDB
Residue 365: 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.Thr365Ala Uncertain significance ★★ ⚠ same residue
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

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-thr365ser (accessed [today's date]).

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