Is PIGW p.Phe57= (c.171C>T) pathogenic?

PIGW p.Phe57= (c.171C>T) is classified Likely benign in PIGW (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). Very rare (popmax 0.000593%, nfe); Associated with hyperphosphatasia with intellectual disability syndrome 5.

What condition is associated with PIGW p.Phe57= (c.171C>T)?

PIGW p.Phe57= (c.171C>T) is associated with hyperphosphatasia with intellectual disability syndrome 5 (ClinVar).

How common is PIGW p.Phe57= (c.171C>T) in the general population?

PIGW p.Phe57= (c.171C>T) is very rare (popmax 0.000593%, nfe) (gnomAD).

PIGW p.Phe57=

Q: How is Hyperphosphatasia-intellectual disability syndrome inherited?

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

c.171C>T · rs1367907051 · VCV2188512

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

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 1.4	GERP 0.74, phastCons 0.78
Overall
CADD	9.544	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,180,022 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,856 alleles · very rare

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.Phe57=
Coding: c.171C>T
MANE Select: NM_001163735 · reported on NM_001346754
dbSNP: rs1367907051
Type: single nucleotide variant
Location: chr17:36537272 (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-phe57 (accessed [today's date]).

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