Is SLC19A2 p.Val18Met (c.52G>A) pathogenic?

SLC19A2 p.Val18Met (c.52G>A) is classified Conflicting classifications of pathogenicity in SLC19A2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-31). AlphaMissense: likely benign (0.1092); Very rare (popmax 0.00119%, sas); Associated with Inborn genetic diseases.

What condition is associated with SLC19A2 p.Val18Met (c.52G>A)?

SLC19A2 p.Val18Met (c.52G>A) is associated with Inborn genetic diseases (ClinVar).

How common is SLC19A2 p.Val18Met (c.52G>A) in the general population?

SLC19A2 p.Val18Met (c.52G>A) is very rare (popmax 0.00119%, sas) (gnomAD).

What do computational predictors say about SLC19A2 p.Val18Met (c.52G>A)?

AlphaMissense predicts likely benign (score 0.1092) — an in-silico prediction, not a clinical call.

SLC19A2 p.Val18Met

c.52G>A · rs574924879 · VCV1519220

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1092 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1092	likely benign
REVEL	0.264	benign-leaning
SaProt	LLR -7.27	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	GERP -3.3
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.054 · regional, not allelic
Overall
CADD	4.616	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 0.00119% South Asian · 1/83,906 alleles

Overall 0.00013% 2/1,539,162 alleles · very rare exomes 2/1,386,856 · genomes 0/152,306 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00119%	83,906
European (non-Finnish)	8.73e-05%	1,145,574

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.Val18Met
Coding: c.52G>A
MANE Select: NM_006996
dbSNP: rs574924879
Type: single nucleotide variant
Location: chr1:169485715 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SLC19A2 p.Val18= Likely benign ★ 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-val18met (accessed [today's date]).

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