Is PIGG p.Pro882= (c.2646A>G) pathogenic?

PIGG p.Pro882= (c.2646A>G) is classified Likely benign in PIGG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-23). No allele count reported in gnomAD v4.1 (AN 1,614,218); Associated with intellectual disability, autosomal recessive 53.

What condition is associated with PIGG p.Pro882= (c.2646A>G)?

PIGG p.Pro882= (c.2646A>G) is associated with intellectual disability, autosomal recessive 53 (ClinVar).

How common is PIGG p.Pro882= (c.2646A>G) in the general population?

PIGG p.Pro882= (c.2646A>G) is no allele count reported in gnomAD v4.1 (AN 1,614,218) (gnomAD).

PIGG p.Pro882=

Q: How is Early-onset epilepsy-intellectual disability-brain anomalies syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.2646A>G · rs1425182590 · VCV1638775

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,218)

Conditions

intellectual disability, autosomal recessive 53

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.22	GERP -5.2, phastCons 0.003
Overall
CADD	3.847	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,614,218). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PIGG
Protein: p.Pro882=
Coding: c.2646A>G
MANE Select: NM_001127178
dbSNP: rs1425182590
Type: single nucleotide variant
Location: chr4:533892 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.48
Residue 882: a UniProt-annotated variant site (in nedhsca); a UniProt-annotated variant site (in nedhsca; loss of ethanolamine phosphate transferase activity as evidenced by abnormal accumulation of the gpi precursors h7 and h7' and absence of mature gpi precursor h8 in patient lymphoblasts); a UniProt-annotated variant site (in nedhsca; decreased protein abundance)

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

Disease context

intellectual disability, autosomal recessive 53 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Early-onset epilepsy-intellectual disability-brain anomalies syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

PIGG p.Pro882Ala Uncertain significance ★ ⚠ same residue
PIGG p.Pro882Ser Uncertain significance ★ ⚠ same residue
PIGG c.570+1G>A Pathogenic/Likely pathogenic ★★ same condition
PIGG p.Arg304Ter Pathogenic ★★ same condition
PIGG p.Arg633Ter Pathogenic/Likely pathogenic ★★ same condition
PIGG p.Gln310Ter Pathogenic ★★ same condition
PIGG p.Gln411Ter Pathogenic/Likely pathogenic ★★ same condition
PIGG p.Gln851Pro Pathogenic/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/pigg-p-pro882 (accessed [today's date]).

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