Is PIGS p.Val469= (c.1407A>G) pathogenic?

PIGS p.Val469= (c.1407A>G) is classified Likely benign in PIGS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-01). Absent from gnomAD v4.1.

How common is PIGS p.Val469= (c.1407A>G) in the general population?

PIGS p.Val469= (c.1407A>G) is absent from gnomAD v4.1 (gnomAD).

PIGS p.Val469=

c.1407A>G · rs2151511094 · VCV1694836

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.54	GERP -2.9, phastCons 0.074
Overall
CADD	1.049	PHRED · no single calibrated threshold — expert panels disagree

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.Val469=
Coding: c.1407A>G
MANE Select: NM_033198
dbSNP: rs2151511094
Type: single nucleotide variant
Location: chr17:28554481 (GRCh38)
Gene constraint: LOEUF 0.76 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48 · 4 PDB
Residue 469: 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); an α-helix

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

Similar variants

PIGS p.Val469Ile Uncertain significance ★ ⚠ same residue
PIGS p.Arg15Trp Uncertain significance ★★ ⚠ same type
PIGS p.Arg176Trp Uncertain significance ★★ ⚠ same type
PIGS p.Arg355Cys Uncertain significance ★★ ⚠ same type
PIGS p.Pro402Ser Uncertain significance ★★ ⚠ same type
PIGS p.Ser224Thr Uncertain significance ★★ ⚠ same type
PIGS p.Tyr522Cys Uncertain significance ★★ ⚠ same type
PIGS p.Val146Met Uncertain significance ★★ ⚠ same type

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-val469 (accessed [today's date]).

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