Is PIGT p.Phe157= (c.471C>T) pathogenic?

PIGT p.Phe157= (c.471C>T) is classified Likely benign in PIGT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-29). Ultra-rare (popmax 0.0428%, sas); Associated with multiple congenital anomalies-hypotonia-seizures syndrome 3.

What condition is associated with PIGT p.Phe157= (c.471C>T)?

PIGT p.Phe157= (c.471C>T) is associated with multiple congenital anomalies-hypotonia-seizures syndrome 3 (ClinVar).

How common is PIGT p.Phe157= (c.471C>T) in the general population?

PIGT p.Phe157= (c.471C>T) is ultra-rare (popmax 0.0428%, sas) (gnomAD).

PIGT p.Phe157=

c.471C>T · rs547812986 · VCV2748769

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0428%, sas)

Conditions

multiple congenital anomalies-hypotonia-seizures syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.111	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1, phastCons 1
Overall
CADD	13.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0428% South Asian · 39/91,080 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0284%

Overall 0.00279% 45/1,614,168 alleles · ultra-rare exomes 44/1,461,842 · genomes 1/152,326 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0428%	2,335
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.000424%	235,999

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: PIGT
Protein: p.Phe157=
Coding: c.471C>T
MANE Select: NM_015937
dbSNP: rs547812986
Type: single nucleotide variant
Location: chr20:45418957 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71 · 4 PDB
Residue 157: a UniProt-annotated variant site (in mcahs3; loss of function in gpi-anchor attachment to protein); a UniProt-annotated variant site (in mcahs3); a UniProt-annotated variant site (in mcahs3; uncertain significance); a β-strand

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

Disease context

multiple congenital anomalies-hypotonia-seizures syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PIGT c.188-2A>G Pathogenic/Likely pathogenic ★★ same condition
PIGT c.494-2A>G Pathogenic ★★ same condition
PIGT p.Arg172Cys Pathogenic/Likely pathogenic ★★ same condition
PIGT p.Arg266Ter Pathogenic/Likely pathogenic ★★ same condition
PIGT p.Arg330Ter Pathogenic ★★ same condition
PIGT p.Arg448Trp Pathogenic/Likely pathogenic ★★ same condition
PIGT p.Glu237Gln Likely pathogenic ★★ same condition
PIGT p.Glu84Ter 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/pigt-p-phe157 (accessed [today's date]).

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