Is SLC19A2 p.Arg275Leu (c.824G>T) pathogenic?

SLC19A2 p.Arg275Leu (c.824G>T) is classified Conflicting classifications of pathogenicity in SLC19A2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-11-27). AlphaMissense: likely benign (0.0952); Rare (popmax 0.332%, afr); Associated with monogenic diabetes.

What condition is associated with SLC19A2 p.Arg275Leu (c.824G>T)?

SLC19A2 p.Arg275Leu (c.824G>T) is associated with monogenic diabetes, thiamine-responsive megaloblastic anemia syndrome (ClinVar).

How common is SLC19A2 p.Arg275Leu (c.824G>T) in the general population?

SLC19A2 p.Arg275Leu (c.824G>T) is rare (popmax 0.332%, afr) (gnomAD).

What do computational predictors say about SLC19A2 p.Arg275Leu (c.824G>T)?

AlphaMissense predicts likely benign (score 0.0952) — an in-silico prediction, not a clinical call.

SLC19A2 p.Arg275Leu

c.824G>T · rs61734338 · VCV393365

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0952 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.332%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

monogenic diabetes

Computational evidence

Protein change
AlphaMissense	0.0952	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -3.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -0.61
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.054 · regional, not allelic
Overall
CADD	13.86	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 0.332% African / African-American · 249/75,004 alleles

Filtering AF 0.298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.285%

Overall 0.0175% 283/1,613,916 alleles · rare exomes 157/1,461,684 · genomes 126/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.332%	301
Admixed American	0.03%	3,332
Remaining individualsnot grpmax-eligible	0.0224%	4,464
South Asian	0.0011%	91,080
European (non-Finnish)	8.48e-05%	1,179,883

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.Arg275Leu
Coding: c.824G>T
MANE Select: NM_006996
dbSNP: rs61734338
Type: single nucleotide variant
Location: chr1:169470170 (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

monogenic diabetes — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: thiamine-responsive megaloblastic anemia syndrome

Similar variants

SLC19A2 p.Arg275Cys Uncertain significance ★★ ⚠ same residue
SLC19A2 p.Arg275His Uncertain significance ★ ⚠ same residue
SLC19A2 p.Arg275= Likely benign ★ 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

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-arg275leu (accessed [today's date]).

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