Is PTS p.Pro98fs (c.292_293insATACTTTG) pathogenic?

PTS p.Pro98fs (c.292293insATACTTTG) is classified Pathogenic in PTS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-22). No gnomAD frequency available for this variant; Associated with BH4-deficient hyperphenylalaninemia A.

What condition is associated with PTS p.Pro98fs (c.292_293insATACTTTG)?

PTS p.Pro98fs (c.292_293insATACTTTG) is associated with BH4-deficient hyperphenylalaninemia A (ClinVar).

How common is PTS p.Pro98fs (c.292_293insATACTTTG) in the general population?

PTS p.Pro98fs (c.292_293insATACTTTG) is no gnomAD frequency available for this variant (gnomAD).

PTS p.Pro98fs

Q: How is Hyperphenylalaninemia due to tetrahydrobiopterin deficiency inherited?

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

c.292_293insATACTTTG · rs2496570916 · VCV2032318

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

BH4-deficient hyperphenylalaninemia A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (5 of 6, 22 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 0.22, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PTS
Protein: p.Pro98fs
Coding: c.292_293insATACTTTG
MANE Select: NM_000317
dbSNP: rs2496570916
Type: Insertion
Location: chr11:112233211 (GRCh38)
Gene constraint: LOEUF 1.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.01 · 1 PDB
Residue 98: an α-helix

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 p.Pro98Gln Uncertain significance ★ ⚠ same residue
PTS p.Pro98Ser Uncertain significance ★ ⚠ same residue
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.243_243+1dup Likely pathogenic ★★ same condition
PTS c.315-1G>A Pathogenic/Likely pathogenic ★★ same condition
PTS c.315-2A>G Pathogenic/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-pro98fs (accessed [today's date]).

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