Is PTS p.Val130= (c.390A>G) pathogenic?

PTS p.Val130= (c.390A>G) is classified Likely benign in PTS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-24). Very rare (popmax 6.2e-05%); Associated with BH4-deficient hyperphenylalaninemia A.

What condition is associated with PTS p.Val130= (c.390A>G)?

PTS p.Val130= (c.390A>G) is associated with BH4-deficient hyperphenylalaninemia A (ClinVar).

How common is PTS p.Val130= (c.390A>G) in the general population?

PTS p.Val130= (c.390A>G) is very rare (popmax 6.2e-05%) (gnomAD).

PTS p.Val130=

Q: How is Hyperphenylalaninemia due to tetrahydrobiopterin deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.390A>G · rs2135410489 · VCV1125349

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

BH4-deficient hyperphenylalaninemia A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.92	GERP -3.1, phastCons 0.99
Overall
CADD	5.462	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,664 alleles · very rare exomes 1/1,461,368 · genomes 0/152,296 · joint denominator

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: PTS
Protein: p.Val130=
Coding: c.390A>G
MANE Select: NM_000317
dbSNP: rs2135410489
Type: single nucleotide variant
Location: chr11:112233507 (GRCh38)
Gene constraint: LOEUF 1.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.01 · 1 PDB
Residue 130: a β-strand

Full PTS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BH4-deficient hyperphenylalaninemia A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperphenylalaninemia due to tetrahydrobiopterin deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Japan)

Similar variants

PTS c.186+1G>A Pathogenic ★★ same condition
PTS c.186+1G>T Pathogenic ★★ same condition
PTS c.187-2A>G Likely pathogenic ★★ same condition
PTS c.315-1G>A Pathogenic/Likely pathogenic ★★ same condition
PTS c.315-2A>G Pathogenic/Likely pathogenic ★★ same condition
PTS c.84-1G>A Likely pathogenic ★★ same condition
PTS c.84-291A>G Pathogenic/Likely pathogenic ★★ same condition
PTS c.84-2A>G Likely 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/pts-p-val130 (accessed [today's date]).

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