Is PIGT p.Pro520= (c.1560G>A) pathogenic?

PIGT p.Pro520= (c.1560G>A) is classified Likely benign in PIGT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-13). Ultra-rare (popmax 0.0379%, eas); Associated with multiple congenital anomalies-hypotonia-seizures syndrome 3.

What condition is associated with PIGT p.Pro520= (c.1560G>A)?

PIGT p.Pro520= (c.1560G>A) is associated with multiple congenital anomalies-hypotonia-seizures syndrome 3 (ClinVar).

How common is PIGT p.Pro520= (c.1560G>A) in the general population?

PIGT p.Pro520= (c.1560G>A) is ultra-rare (popmax 0.0379%, eas) (gnomAD).

PIGT p.Pro520=

c.1560G>A · rs566450064 · VCV2911529

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, eas)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.2	GERP -4.9
Overall
CADD	6.075	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0379% East Asian · 17/44,856 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.00118% 19/1,614,072 alleles · ultra-rare exomes 13/1,461,822 · genomes 6/152,250 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0379%	2,639
European (non-Finnish)	0.000169%	590,002

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.Pro520=
Coding: c.1560G>A
MANE Select: NM_015937
dbSNP: rs566450064
Type: single nucleotide variant
Location: chr20:45425649 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71 · 4 PDB
Residue 520: a UniProt-annotated variant site (in mcahs3; loss of function in gpi-anchor attachment to protein); a UniProt-annotated variant site (in mcahs3)

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-pro520 (accessed [today's date]).

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