Is PYGL p.Arg161Gln (c.482G>A) pathogenic?

PYGL p.Arg161Gln (c.482G>A) is classified Uncertain significance in PYGL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-04). AlphaMissense: likely pathogenic (0.8289); Ultra-rare (popmax 0.0296%, sas); Associated with Inborn genetic diseases.

What condition is associated with PYGL p.Arg161Gln (c.482G>A)?

PYGL p.Arg161Gln (c.482G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PYGL p.Arg161Gln (c.482G>A) in the general population?

PYGL p.Arg161Gln (c.482G>A) is ultra-rare (popmax 0.0296%, sas) (gnomAD).

What do computational predictors say about PYGL p.Arg161Gln (c.482G>A)?

AlphaMissense predicts likely pathogenic (score 0.8289) — an in-silico prediction, not a clinical call.

PYGL p.Arg161Gln

c.482G>A · VCV3941379

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8289 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0296%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8289	likely pathogenic
REVEL	0.951	strongly pathogenic-leaning
SaProt	LLR -9.59	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 39 kb · p 0.2 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0296% South Asian · 27/91,068 alleles

Filtering AF 0.0208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.018%

Overall 0.00297% 48/1,613,896 alleles · ultra-rare exomes 41/1,461,738 · genomes 7/152,158 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0296%	3,373
East Asian	0.00669%	14,956
African / African-American	0.004%	24,998
Remaining individualsnot grpmax-eligible	0.0032%	31,250
European (non-Finnish)	0.0011%	90,763

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: PYGL
Protein: p.Arg161Gln
Coding: c.482G>A
MANE Select: NM_002863
Type: single nucleotide variant
Location: chr14:50931719 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.87 · 19 PDB

Full PYGL 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

PYGL p.Arg161Trp Uncertain significance ★★ ⚠ same residue
PYGL p.Ala108Thr Uncertain significance ★★ ⚠ same condition
PYGL p.Ala704Thr Uncertain significance ★★ ⚠ same condition
PYGL p.Asn847Ile Uncertain significance ★★ ⚠ same condition
PYGL p.Asp110Val Uncertain significance ★★ ⚠ same condition
PYGL p.Asp528Asn Uncertain significance ★★ ⚠ same condition
PYGL p.Gly159Ser Uncertain significance ★★ ⚠ same condition
PYGL p.Gly449Ser 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/pygl-p-arg161gln (accessed [today's date]).

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