Is PIGW p.Pro51= (c.153T>C) pathogenic?

PIGW p.Pro51= (c.153T>C) is classified Likely benign in PIGW (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). Very rare (popmax 0.00549%, sas); Associated with hyperphosphatasia with intellectual disability syndrome 5.

What condition is associated with PIGW p.Pro51= (c.153T>C)?

PIGW p.Pro51= (c.153T>C) is associated with hyperphosphatasia with intellectual disability syndrome 5 (ClinVar).

How common is PIGW p.Pro51= (c.153T>C) in the general population?

PIGW p.Pro51= (c.153T>C) is very rare (popmax 0.00549%, sas) (gnomAD).

PIGW p.Pro51=

Q: How is Hyperphosphatasia-intellectual disability syndrome inherited?

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

c.153T>C · rs748068199 · VCV1668783

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

hyperphosphatasia with intellectual disability syndrome 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.43	GERP -1.8
Overall
CADD	8.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,092 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000805% 13/1,614,036 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,218
East Asian	0.00445%	22,449
European (non-Finnish)	0.000508%	196,671

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: PIGW
Protein: p.Pro51=
Coding: c.153T>C
MANE Select: NM_001163735 · reported on NM_001346754
dbSNP: rs748068199
Type: single nucleotide variant
Location: chr17:36537254 (GRCh38)

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

Disease context

hyperphosphatasia with intellectual disability syndrome 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperphosphatasia-intellectual disability syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

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/pigw-p-pro51 (accessed [today's date]).

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