Is PIGS p.Pro329Arg (c.986C>G) pathogenic?

PIGS p.Pro329Arg (c.986C>G) is classified Pathogenic in PIGS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-05-21). AlphaMissense: likely pathogenic (0.9745); Absent from gnomAD v4.1; Associated with glycosylphosphatidylinositol biosynthesis defect 18.

What condition is associated with PIGS p.Pro329Arg (c.986C>G)?

PIGS p.Pro329Arg (c.986C>G) is associated with glycosylphosphatidylinositol biosynthesis defect 18 (ClinVar).

How common is PIGS p.Pro329Arg (c.986C>G) in the general population?

PIGS p.Pro329Arg (c.986C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PIGS p.Pro329Arg (c.986C>G)?

AlphaMissense predicts likely pathogenic (score 0.9745) — an in-silico prediction, not a clinical call.

PIGS p.Pro329Arg

c.986C>G · rs2151511848 · VCV1119955

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9745 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycosylphosphatidylinositol biosynthesis defect 18

Computational evidence

Protein change
AlphaMissense	0.9745	likely pathogenic ✓ concordant with ClinVar · top 5% in PIGS
REVEL	0.938	strongly pathogenic-leaning
SaProt	LLR -15.57	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 17 kb · p 0.0022 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PIGS
Protein: p.Pro329Arg
Coding: c.986C>G
MANE Select: NM_033198
dbSNP: rs2151511848
Type: single nucleotide variant
Location: chr17:28556921 (GRCh38)
Gene constraint: LOEUF 0.76 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48 · 4 PDB
Residue 329: a UniProt-annotated variant site (in gpibd18; almost complete loss of function; when tested in pigs-knockout cells, mediates only very partial restoration of gpi-anchored protein expression at the cell surface; strong decrease in protein level, possibly due to nonsense-mediated mrna decay)

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

Disease context

glycosylphosphatidylinositol biosynthesis defect 18 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PIGS p.Arg176Trp Uncertain significance ★★ ⚠ same condition
PIGS p.Pro402Ser Uncertain significance ★★ ⚠ same condition
PIGS p.Leu34Pro Likely pathogenic ★ same condition
PIGS p.Leu479Ter Likely pathogenic ★ same condition
PIGS p.Trp245Ter Pathogenic ★ same condition
PIGS p.Trp36Ter Likely pathogenic ★ same condition
PIGS p.Arg184Cys Uncertain significance ★ ⚠ same condition
PIGS p.Arg425Gln 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/pigs-p-pro329arg (accessed [today's date]).

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