Is PIGO p.Ser830= (c.2490T>C) pathogenic?

PIGO p.Ser830= (c.2490T>C) is classified Likely benign in PIGO (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-21). Very rare (popmax 0.00935%, afr); Associated with hyperphosphatasia with intellectual disability syndrome 2.

What condition is associated with PIGO p.Ser830= (c.2490T>C)?

PIGO p.Ser830= (c.2490T>C) is associated with hyperphosphatasia with intellectual disability syndrome 2 (ClinVar).

How common is PIGO p.Ser830= (c.2490T>C) in the general population?

PIGO p.Ser830= (c.2490T>C) is very rare (popmax 0.00935%, afr) (gnomAD).

PIGO p.Ser830=

Q: How is Hyperphosphatasia-intellectual disability syndrome inherited?

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

c.2490T>C · VCV3675694

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Conditions

hyperphosphatasia with intellectual disability syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.9	GERP -3.1
Overall
CADD	0.936	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,828 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000496% 8/1,613,814 alleles · very rare exomes 3/1,461,880 · genomes 5/151,934 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,690
European (non-Finnish)	8.47e-05%	1,180,004

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: PIGO
Protein: p.Ser830=
Coding: c.2490T>C
MANE Select: NM_032634
Type: single nucleotide variant
Location: chr9:35091397 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.57
Residue 830: a UniProt-annotated variant site (in hpmrs2)

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.Ser830Gly Uncertain significance ★ ⚠ same residue
PIGO c.2648-1G>A Likely pathogenic ★★ same condition
PIGO c.3069+2T>C Likely pathogenic ★★ same condition
PIGO c.3069+5G>A Pathogenic/Likely pathogenic ★★ same condition
PIGO p.Arg119Trp Likely pathogenic ★★ ⚠ same condition
PIGO p.Arg122Ter Pathogenic/Likely pathogenic ★★ same condition
PIGO p.Arg376Ter Pathogenic/Likely pathogenic ★★ same condition
PIGO p.Arg802Ter 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/pigo-p-ser830 (accessed [today's date]).

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