Is SLC19A2 p.Met380Thr (c.1139T>C) pathogenic?

SLC19A2 p.Met380Thr (c.1139T>C) is classified Uncertain significance in SLC19A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-18). AlphaMissense: ambiguous (0.3821); Ultra-rare (popmax 0.028%, afr); Associated with Inborn genetic diseases.

What condition is associated with SLC19A2 p.Met380Thr (c.1139T>C)?

SLC19A2 p.Met380Thr (c.1139T>C) is associated with Inborn genetic diseases (ClinVar).

How common is SLC19A2 p.Met380Thr (c.1139T>C) in the general population?

SLC19A2 p.Met380Thr (c.1139T>C) is ultra-rare (popmax 0.028%, afr) (gnomAD).

What do computational predictors say about SLC19A2 p.Met380Thr (c.1139T>C)?

AlphaMissense predicts ambiguous (score 0.3821) — an in-silico prediction, not a clinical call.

SLC19A2 p.Met380Thr

c.1139T>C · rs375188929 · VCV1398076

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3821 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3821	ambiguous
REVEL	0.848	moderately pathogenic-leaning
SaProt	LLR -9.22	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.054 · regional, not allelic
Overall
CADD	26.3	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 0.028% African / African-American · 21/74,926 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00143% 23/1,613,782 alleles · ultra-rare exomes 10/1,461,568 · genomes 13/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.028%	3,568
Admixed American	0.00167%	59,998
European (non-Finnish)	8.48e-05%	1,179,800

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.Met380Thr
Coding: c.1139T>C
MANE Select: NM_006996
dbSNP: rs375188929
Type: single nucleotide variant
Location: chr1:169468728 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 2 PDB
Residue 380: an α-helix

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

Similar variants

SLC19A2 p.Met380Ile Uncertain significance ★ ⚠ same residue
SLC19A2 p.Ala201Gly Uncertain significance ★★ ⚠ same condition
SLC19A2 p.Ala431Ser Uncertain significance ★★ ⚠ same condition
SLC19A2 p.Arg275Cys Uncertain significance ★★ ⚠ same condition
SLC19A2 p.Glu321Lys Uncertain significance ★★ same condition
SLC19A2 p.Gly184Ser Uncertain significance ★★ ⚠ same condition
SLC19A2 p.Gly235Ser Uncertain significance ★★ ⚠ same condition
SLC19A2 p.Gly362Glu Uncertain significance ★★ ⚠ 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-met380thr (accessed [today's date]).

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