Is PIGA p.Lys293= (c.879G>A) pathogenic?

PIGA p.Lys293= (c.879G>A) is classified Benign/Likely benign in PIGA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-13). Ultra-rare (popmax 0.0385%, amr); Associated with multiple congenital anomalies-hypotonia-seizures syndrome 2.

What condition is associated with PIGA p.Lys293= (c.879G>A)?

PIGA p.Lys293= (c.879G>A) is associated with multiple congenital anomalies-hypotonia-seizures syndrome 2 (ClinVar).

How common is PIGA p.Lys293= (c.879G>A) in the general population?

PIGA p.Lys293= (c.879G>A) is ultra-rare (popmax 0.0385%, amr) (gnomAD).

PIGA p.Lys293=

c.879G>A · rs777674120 · VCV387505

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0385%, amr)

Conditions

multiple congenital anomalies-hypotonia-seizures syndrome 2

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 1.4	GERP 1.9, phastCons 1
Overall
CADD	8.916	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0385% Admixed American · 17/44,178 alleles

Filtering AF 0.0244% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.02%

Overall 0.00158% 19/1,200,791 alleles · ultra-rare exomes 19/1,087,040 · genomes 0/113,751 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0385%	2,599
European (non-Finnish)	0.000225%	445,270

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: PIGA
Protein: p.Lys293=
Coding: c.879G>A
MANE Select: NM_002641
dbSNP: rs777674120
Type: single nucleotide variant
Location: chrX:15325122 (GRCh38)
Structure: AlphaFold pLDDT 86.22

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

Disease context

multiple congenital anomalies-hypotonia-seizures syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PIGA p.Lys293Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
PIGA p.Arg119Gln Pathogenic/Likely pathogenic ★★ same condition
PIGA p.Arg119Trp Pathogenic/Likely pathogenic ★★ same condition
PIGA p.Arg412Ter Pathogenic ★★ same condition
PIGA p.Arg81His Likely pathogenic ★★ same condition
PIGA p.Val329Ala Likely pathogenic ★★ same condition
PIGA p.Val49Met Pathogenic/Likely pathogenic ★★ same condition
PIGA c.982-3A>C 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/piga-p-lys293 (accessed [today's date]).

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