Is PIGL p.Lys89Arg (c.266A>G) pathogenic?

PIGL p.Lys89Arg (c.266A>G) is classified Uncertain significance in PIGL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.0963); Very rare (popmax 0.00934%, afr); Associated with Inborn genetic diseases.

What condition is associated with PIGL p.Lys89Arg (c.266A>G)?

PIGL p.Lys89Arg (c.266A>G) is associated with Inborn genetic diseases (ClinVar).

How common is PIGL p.Lys89Arg (c.266A>G) in the general population?

PIGL p.Lys89Arg (c.266A>G) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about PIGL p.Lys89Arg (c.266A>G)?

AlphaMissense predicts likely benign (score 0.0963) — an in-silico prediction, not a clinical call.

PIGL p.Lys89Arg

c.266A>G · VCV4136568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0963 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0963	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -6.73	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 109 kb · p 0.43 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,954 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000497% 8/1,609,704 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,708
South Asian	0.0011%	90,986

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.Lys89Arg
Coding: c.266A>G
MANE Select: NM_004278
Type: single nucleotide variant
Location: chr17:16234001 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PIGL p.Ala54Val Uncertain significance ★★ ⚠ same condition
PIGL p.Arg245Lys Uncertain significance ★★ ⚠ same condition
PIGL p.Asp116Asn Uncertain significance ★★ ⚠ same condition
PIGL p.Asp147Asn Uncertain significance ★★ ⚠ same condition
PIGL p.His203Asp Uncertain significance ★★ ⚠ same condition
PIGL p.Leu202Pro Uncertain significance ★★ ⚠ same condition
PIGL p.Leu6Arg Uncertain significance ★★ ⚠ same condition
PIGL p.Met55Val 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-lys89arg (accessed [today's date]).

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