Is PIGS p.Ter556= (c.1667G>A) pathogenic?

PIGS p.Ter556= (c.1667G>A) is classified Likely benign in PIGS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-07). Rare (popmax 0.24%, amr); Associated with PIGS-related disorder.

What condition is associated with PIGS p.Ter556= (c.1667G>A)?

PIGS p.Ter556= (c.1667G>A) is associated with PIGS-related disorder (ClinVar).

How common is PIGS p.Ter556= (c.1667G>A) in the general population?

PIGS p.Ter556= (c.1667G>A) is rare (popmax 0.24%, amr) (gnomAD).

PIGS p.Ter556=

c.1667G>A · rs778022172 · VCV3045738

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.24%, amr)

Conditions

PIGS-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.53, phastCons 1
Overall
CADD	10.53	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.24% Admixed American · 144/60,006 alleles

Filtering AF 0.208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.196%

Overall 0.00905% 146/1,613,816 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.24%	417
Remaining individualsnot grpmax-eligible	0.0032%	31,241

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: PIGS
Protein: p.Ter556=
Coding: c.1667G>A
MANE Select: NM_033198
dbSNP: rs778022172
Type: single nucleotide variant
Location: chr17:28554221 (GRCh38)
Gene constraint: LOEUF 0.76 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48 · 4 PDB

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

Disease context

PIGS-related disorder

Similar variants

PIGS c.1081-2A>T Likely pathogenic ★ same condition
PIGS c.1392+1G>A Likely pathogenic ★ same condition
PIGS p.Tyr96Ter Likely pathogenic ★ same condition
PIGS c.286+7T>C Benign same condition
PIGS p.Arg185His Likely benign same condition
PIGS p.Glu72Ala Benign same condition
PIGS p.Arg15Trp Uncertain significance ★★ same type
PIGS p.Arg176Trp 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-ter556 (accessed [today's date]).

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