Is PIGL p.Phe209= (c.627C>T) pathogenic?

PIGL p.Phe209= (c.627C>T) is classified Conflicting classifications of pathogenicity in PIGL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-22). Ultra-rare (popmax 0.0306%, afr); Associated with CHIME syndrome.

What condition is associated with PIGL p.Phe209= (c.627C>T)?

PIGL p.Phe209= (c.627C>T) is associated with CHIME syndrome (ClinVar).

How common is PIGL p.Phe209= (c.627C>T) in the general population?

PIGL p.Phe209= (c.627C>T) is ultra-rare (popmax 0.0306%, afr) (gnomAD).

PIGL p.Phe209=

c.627C>T · rs146164310 · VCV159717

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0306%, afr)

Conditions

CHIME syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.319	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6	GERP -3.5
Overall
CADD	1.876	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0306% African / African-American · 23/75,050 alleles

Filtering AF 0.0209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0177%

Overall 0.00248% 40/1,613,880 alleles · ultra-rare exomes 28/1,461,550 · genomes 12/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0306%	3,263
Remaining individualsnot grpmax-eligible	0.0224%	4,464
Admixed American	0.00167%	60,028
South Asian	0.0011%	91,072
European (non-Finnish)	8.47e-05%	1,180,040

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.Phe209=
Coding: c.627C>T
MANE Select: NM_004278
dbSNP: rs146164310
Type: single nucleotide variant
Location: chr17:16317875 (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-phe209 (accessed [today's date]).

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