Is PIGO p.Phe299fs (c.894_895del) pathogenic?

PIGO p.Phe299fs (c.894895del) is classified Pathogenic in PIGO (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-18). No gnomAD frequency available for this variant; Associated with hyperphosphatasia with intellectual disability syndrome 2.

What condition is associated with PIGO p.Phe299fs (c.894_895del)?

PIGO p.Phe299fs (c.894_895del) is associated with hyperphosphatasia with intellectual disability syndrome 2 (ClinVar).

How common is PIGO p.Phe299fs (c.894_895del) in the general population?

PIGO p.Phe299fs (c.894_895del) is no gnomAD frequency available for this variant (gnomAD).

PIGO p.Phe299fs

Q: How is Hyperphosphatasia-intellectual disability syndrome inherited?

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

c.894_895del · rs2490463730 · VCV1903867

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

hyperphosphatasia with intellectual disability syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.7, 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: PIGO
Protein: p.Phe299fs
Coding: c.894_895del
MANE Select: NM_032634
dbSNP: rs2490463730
Type: Microsatellite
Location: chr9:35093465 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.57

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

Disease context

hyperphosphatasia with intellectual disability syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperphosphatasia-intellectual disability syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

PIGO p.Val424fs Pathogenic/Likely pathogenic ★★ same condition
PIGO p.Leu554del Uncertain significance ★★ same condition
PIGO p.Leu868fs Pathogenic ★ same condition
PIGO p.Leu949del Uncertain significance ★ same condition
PIGO c.3070-12CTC[2] Likely benign ★ same condition
PIGO c.3070-14_3070-12del Likely benign ★ same condition
PIGO c.2648-1G>A Likely pathogenic ★★ same condition
PIGO c.3069+2T>C 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/pigo-p-phe299fs (accessed [today's date]).

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