Is PIGL p.Pro118= (c.354A>G) pathogenic?

PIGL p.Pro118= (c.354A>G) is classified Conflicting classifications of pathogenicity in PIGL (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-10-09). Rare (popmax 0.975%, mid); Associated with CHIME syndrome.

What condition is associated with PIGL p.Pro118= (c.354A>G)?

PIGL p.Pro118= (c.354A>G) is associated with CHIME syndrome (ClinVar).

How common is PIGL p.Pro118= (c.354A>G) in the general population?

PIGL p.Pro118= (c.354A>G) is rare (popmax 0.975%, mid) (gnomAD).

PIGL p.Pro118=

c.354A>G · rs149094276 · VCV159704

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.975%, mid)

Conditions

CHIME syndrome

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 -0.21	GERP -3.5
Overall
CADD	2.931	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.975% Middle Eastern · 59/6,052 alleles

Filtering AF 0.776% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.704%

Overall 0.0162% 262/1,613,726 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.975%	103
Admixed American	0.0167%	6,001
European (non-Finnish)	0.0148%	6,779
Remaining individualsnot grpmax-eligible	0.0144%	6,944
South Asian	0.00549%	18,217
African / African-American	0.00533%	18,763
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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: PIGL
Protein: p.Pro118=
Coding: c.354A>G
MANE Select: NM_004278
dbSNP: rs149094276
Type: single nucleotide variant
Location: chr17:16299906 (GRCh38)
Gene constraint: LOEUF 1.239 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.66

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

Disease context

CHIME syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PIGL c.427-1G>A Pathogenic ★★ same condition
PIGL c.660+1G>T Likely pathogenic ★★ same condition
PIGL p.Arg88Cys Likely pathogenic ★★ same condition
PIGL p.Leu167Pro Pathogenic ★★ same condition
PIGL p.Arg165= Uncertain significance ★★ same condition
PIGL p.Arg242Pro Uncertain significance ★★ ⚠ same condition
PIGL p.Arg242Trp Uncertain significance ★★ ⚠ same condition
PIGL p.Arg88His 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/pigl-p-pro118 (accessed [today's date]).

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