Is PIGT p.Arg27= (c.81C>G) pathogenic?

PIGT p.Arg27= (c.81C>G) is classified Likely benign in PIGT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-08). Very rare (popmax 0.00134%, afr); Associated with multiple congenital anomalies-hypotonia-seizures syndrome 3.

What condition is associated with PIGT p.Arg27= (c.81C>G)?

PIGT p.Arg27= (c.81C>G) is associated with multiple congenital anomalies-hypotonia-seizures syndrome 3 (ClinVar).

How common is PIGT p.Arg27= (c.81C>G) in the general population?

PIGT p.Arg27= (c.81C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

PIGT p.Arg27=

c.81C>G · rs2515512481 · VCV2003377

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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	0.037	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 0.39, phastCons 1
Overall
CADD	14.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,650 alleles

Overall 6.93e-05% 1/1,443,722 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: PIGT
Protein: p.Arg27=
Coding: c.81C>G
MANE Select: NM_015937
dbSNP: rs2515512481
Type: single nucleotide variant
Location: chr20:45416237 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71 · 4 PDB
Residue 27: 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 p.Arg27Ser Uncertain significance ★ ⚠ same residue
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

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-arg27 (accessed [today's date]).

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