Is PYGM p.Phe599fs (c.1797del) pathogenic?

PYGM p.Phe599fs (c.1797del) is classified Pathogenic/Likely pathogenic in PYGM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-08-31). Very rare (popmax 0.0011%, nfe); Associated with PYGM-related disorder.

What condition is associated with PYGM p.Phe599fs (c.1797del)?

PYGM p.Phe599fs (c.1797del) is associated with PYGM-related disorder, glycogen storage disease V (ClinVar).

How common is PYGM p.Phe599fs (c.1797del) in the general population?

PYGM p.Phe599fs (c.1797del) is very rare (popmax 0.0011%, nfe) (gnomAD).

PYGM p.Phe599fs

c.1797del · rs769960481 · VCV188807

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Conditions

PYGM-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,179,900 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000929% 15/1,613,988 alleles · very rare exomes 15/1,461,698 · genomes 0/152,290 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)grpmax	0.0011%	90,761
South Asian	0.0011%	91,084

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PYGM
Protein: p.Phe599fs
Coding: c.1797del
MANE Select: NM_005609
dbSNP: rs769960481
Type: Deletion
Location: chr11:64751627 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 599: a UniProt-annotated variant site (in gsd5)

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

Disease context

PYGM-related disorder

Also linked: glycogen storage disease V

Similar variants

PYGM c.2177_2177+3del Likely pathogenic ★★ same condition
PYGM p.Ala55fs Pathogenic ★★ same condition
PYGM p.Arg161_Tyr162insTer Pathogenic/Likely pathogenic ★★ same condition
PYGM p.Arg194fs Pathogenic/Likely pathogenic ★★ same condition
PYGM p.Asn454_Leu464del Pathogenic/Likely pathogenic ★★ same condition
PYGM p.Glu125fs Pathogenic ★★ same condition
PYGM p.Glu27fs Pathogenic ★★ same condition
PYGM p.Glu797fs Pathogenic ★★ 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/pygm-p-phe599fs (accessed [today's date]).

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