Is PIGA p.Asp153= (c.459C>T) pathogenic?

PIGA p.Asp153= (c.459C>T) is classified Likely benign in PIGA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-09). Very rare (popmax 0.00174%, afr); Associated with multiple congenital anomalies-hypotonia-seizures syndrome 2.

What condition is associated with PIGA p.Asp153= (c.459C>T)?

PIGA p.Asp153= (c.459C>T) is associated with multiple congenital anomalies-hypotonia-seizures syndrome 2 (ClinVar).

How common is PIGA p.Asp153= (c.459C>T) in the general population?

PIGA p.Asp153= (c.459C>T) is very rare (popmax 0.00174%, afr) (gnomAD).

PIGA p.Asp153=

c.459C>T · rs1922153058 · VCV1083999

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00174%, afr)

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 3.4	GERP -1.6, phastCons 1
Overall
CADD	7.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00174% African / African-American · 1/57,324 alleles

Overall 8.26e-05% 1/1,210,633 alleles · very rare exomes 0/1,098,103 · genomes 1/112,530 · joint denominator

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.Asp153=
Coding: c.459C>T
MANE Select: NM_002641
dbSNP: rs1922153058
Type: single nucleotide variant
Location: chrX:15331472 (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.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
PIGA p.Ala2Thr 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-asp153 (accessed [today's date]).

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