Is PIGT p.Pro348fs (c.1043del) pathogenic?

PIGT p.Pro348fs (c.1043del) is classified Pathogenic in PIGT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). Very rare (popmax 0.0017%, nfe); Associated with multiple congenital anomalies-hypotonia-seizures syndrome 3.

What condition is associated with PIGT p.Pro348fs (c.1043del)?

PIGT p.Pro348fs (c.1043del) is associated with multiple congenital anomalies-hypotonia-seizures syndrome 3 (ClinVar).

How common is PIGT p.Pro348fs (c.1043del) in the general population?

PIGT p.Pro348fs (c.1043del) is very rare (popmax 0.0017%, nfe) (gnomAD).

PIGT p.Pro348fs

c.1043del · rs749895437 · VCV2995955

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0017%, nfe)

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.6	GERP -3.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0017% European (non-Finnish) · 20/1,178,872 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000901%

Overall 0.00144% 21/1,460,154 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0017%	58,943
Remaining individualsnot grpmax-eligible	0.0016%	62,434

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.Pro348fs
Coding: c.1043del
MANE Select: NM_015937
dbSNP: rs749895437
Type: Deletion
Location: chr20:45421386 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71 · 4 PDB
Residue 348: a UniProt-annotated variant site (in mcahs3; loss of function in gpi-anchor attachment to protein); a UniProt-annotated variant site (in mcahs3); an α-helix

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 p.Leu134fs Likely pathogenic ★ same condition
PIGT p.Pro6fs Likely pathogenic ★ same condition
PIGT p.Trp189fs Pathogenic ★ same condition
PIGT p.Trp20fs Pathogenic ★ same condition
PIGT p.Pro348Leu Uncertain significance ★ ⚠ same residue
PIGT p.Pro577fs Uncertain significance ★ same condition
PIGT c.188-2A>G Pathogenic/Likely pathogenic ★★ same condition
PIGT c.494-2A>G 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-pro348fs (accessed [today's date]).

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