Is SLC19A2 p.Val88Met (c.262G>A) pathogenic?

SLC19A2 p.Val88Met (c.262G>A) is classified Uncertain significance in SLC19A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-08). AlphaMissense: ambiguous (0.4483); Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with SLC19A2 p.Val88Met (c.262G>A)?

SLC19A2 p.Val88Met (c.262G>A) is associated with Inborn genetic diseases (ClinVar).

How common is SLC19A2 p.Val88Met (c.262G>A) in the general population?

SLC19A2 p.Val88Met (c.262G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about SLC19A2 p.Val88Met (c.262G>A)?

AlphaMissense predicts ambiguous (score 0.4483) — an in-silico prediction, not a clinical call.

SLC19A2 p.Val88Met

c.262G>A · rs763545818 · VCV1978443

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4483 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4483	ambiguous
REVEL	0.63	indeterminate
SaProt	LLR -12.01	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.1, 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 0.00439% South Asian · 4/91,048 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000496% 8/1,612,418 alleles · very rare exomes 8/1,461,776 · genomes 0/150,642 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,762
European (non-Finnish)	0.000339%	294,948

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.Val88Met
Coding: c.262G>A
MANE Select: NM_006996
dbSNP: rs763545818
Type: single nucleotide variant
Location: chr1:169477700 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 2 PDB
Residue 88: 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.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
SLC19A2 p.Gly447Ser 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-val88met (accessed [today's date]).

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