Is PYGM p.Arg804Pro (c.2411G>C) pathogenic?

PYGM p.Arg804Pro (c.2411G>C) is classified Uncertain significance in PYGM (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-12). AlphaMissense: likely pathogenic (0.9589); Very rare (popmax 0.0011%, sas).

How common is PYGM p.Arg804Pro (c.2411G>C) in the general population?

PYGM p.Arg804Pro (c.2411G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about PYGM p.Arg804Pro (c.2411G>C)?

AlphaMissense predicts likely pathogenic (score 0.9589) — an in-silico prediction, not a clinical call.

PYGM p.Arg804Pro

c.2411G>C · rs372295369 · VCV1306482

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9589 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9589	likely pathogenic
REVEL	0.785	moderately pathogenic-leaning
SaProt	LLR -16.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -0.47, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 13 kb · p 0.00017 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0011% South Asian · 1/91,088 alleles

Overall 6.2e-05% 1/1,614,124 alleles · very rare exomes 1/1,461,894 · genomes 0/152,230 · joint denominator

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.Arg804Pro
Coding: c.2411G>C
MANE Select: NM_005609
dbSNP: rs372295369
Type: single nucleotide variant
Location: chr11:64746777 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 804: an α-helix; a UniProt-annotated variant site (in gsd5)

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

Similar variants

PYGM p.Arg804Gln Uncertain significance ★★ ⚠ same residue
PYGM p.Arg804= Likely benign ★ same residue
PYGM c.1092+1G>A Likely pathogenic ★★ same type
PYGM c.1092+1G>C Likely pathogenic ★★ same type
PYGM c.1239+1G>A Pathogenic/Likely pathogenic ★★ same type
PYGM c.1240-2A>G Likely pathogenic ★★ same type
PYGM c.1403+1G>A Pathogenic ★★ same type
PYGM c.1768+1G>A Pathogenic/Likely pathogenic ★★ same type

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-arg804pro (accessed [today's date]).

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