Is PIGW p.Phe49= (c.147T>C) pathogenic?

PIGW p.Phe49= (c.147T>C) is classified Likely benign in PIGW (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-19). Absent from gnomAD v4.1; Associated with hyperphosphatasia with intellectual disability syndrome 5.

What condition is associated with PIGW p.Phe49= (c.147T>C)?

PIGW p.Phe49= (c.147T>C) is associated with hyperphosphatasia with intellectual disability syndrome 5 (ClinVar).

How common is PIGW p.Phe49= (c.147T>C) in the general population?

PIGW p.Phe49= (c.147T>C) is absent from gnomAD v4.1 (gnomAD).

PIGW p.Phe49=

Q: How is Hyperphosphatasia-intellectual disability syndrome inherited?

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

c.147T>C · rs2142614109 · VCV2099691

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.24	GERP -1.4, phastCons 0.19
Overall
CADD	6.719	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PIGW
Protein: p.Phe49=
Coding: c.147T>C
MANE Select: NM_001346754
dbSNP: rs2142614109
Type: single nucleotide variant
Location: chr17:36537248 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.17

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

Similar variants

PIGW p.Ala301Ser Uncertain significance ★★ ⚠ same condition
PIGW p.Ala379Asp Uncertain significance ★★ ⚠ same condition
PIGW p.Arg187Lys Uncertain significance ★★ ⚠ same condition
PIGW p.Arg216Gln Uncertain significance ★★ ⚠ same condition
PIGW p.Arg330Leu Uncertain significance ★★ ⚠ same condition
PIGW p.Arg366Gln Uncertain significance ★★ ⚠ same condition
PIGW p.Asn259Ser Uncertain significance ★★ ⚠ same condition
PIGW p.Asn420Thr Uncertain significance ★★ ⚠ 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/pigw-p-phe49 (accessed [today's date]).

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