Is SLC19A2 p.Arg327Leu (c.980G>T) pathogenic?

SLC19A2 p.Arg327Leu (c.980G>T) is classified Uncertain significance in SLC19A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-03-03). AlphaMissense: likely benign (0.1152); Very rare (popmax 0.00134%, afr); Associated with monogenic diabetes.

What condition is associated with SLC19A2 p.Arg327Leu (c.980G>T)?

SLC19A2 p.Arg327Leu (c.980G>T) is associated with monogenic diabetes (ClinVar).

How common is SLC19A2 p.Arg327Leu (c.980G>T) in the general population?

SLC19A2 p.Arg327Leu (c.980G>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about SLC19A2 p.Arg327Leu (c.980G>T)?

AlphaMissense predicts likely benign (score 0.1152) — an in-silico prediction, not a clinical call.

SLC19A2 p.Arg327Leu

c.980G>T · rs756708244 · VCV549507

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1152 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

monogenic diabetes

Computational evidence

Protein change
AlphaMissense	0.1152	likely benign
REVEL	0.227	benign-leaning
SaProt	LLR -9.70	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 0.47	GERP 1.2, phastCons 0.047
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.054 · regional, not allelic
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,836 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000744% 12/1,613,774 alleles · very rare exomes 11/1,461,728 · genomes 1/152,046 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,836
European (non-Finnish)	0.000932%	107,265

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.Arg327Leu
Coding: c.980G>T
MANE Select: NM_006996
dbSNP: rs756708244
Type: single nucleotide variant
Location: chr1:169470014 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 2 PDB
Residue 327: a β-strand

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

Similar variants

SLC19A2 p.Arg327Cys Uncertain significance ★★ ⚠ same residue
SLC19A2 p.Arg327= Likely benign ★ same residue
SLC19A2 p.Val266Met Benign ★★ same condition
SLC19A2 p.Arg275Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
SLC19A2 p.Val426Ile Conflicting classifications of pathogenicity ★ ⚠ same condition
SLC19A2 c.1223+1G>A Pathogenic ★★ same type
SLC19A2 c.807+2T>G Likely pathogenic ★★ same type
SLC19A2 p.Arg162Ter Pathogenic ★★ same type

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-arg327leu (accessed [today's date]).

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