Is PGAM5 p.Pro55Arg (c.164C>G) pathogenic?

PGAM5 p.Pro55Arg (c.164C>G) is classified Uncertain significance in PGAM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-30). AlphaMissense: likely benign (0.0832); Absent from gnomAD v4.1.

How common is PGAM5 p.Pro55Arg (c.164C>G) in the general population?

PGAM5 p.Pro55Arg (c.164C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PGAM5 p.Pro55Arg (c.164C>G)?

AlphaMissense predicts likely benign (score 0.0832) — an in-silico prediction, not a clinical call.

PGAM5 p.Pro55Arg

c.164C>G · rs2043516726 · VCV2309665

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0832 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0832	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -9.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.93	phastCons 0.41
Regional constraint	o/e 0.94	unconstrained · MANE · 9,948 bp · p 0.22 · regional, not allelic
Overall
CADD	14.27	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PGAM5
Protein: p.Pro55Arg
Coding: c.164C>G
MANE Select: NM_001170543
dbSNP: rs2043516726
Type: single nucleotide variant
Location: chr12:132711040 (GRCh38)
Gene constraint: LOEUF 1.395 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.94 · 10 PDB
Residue 55: the 'disordered' region

Full PGAM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PGAM5 c.191+177G>A Benign ★★ same type
PGAM5 c.191+68A>G Benign ★★ same type
PGAM5 c.497-65G>T Benign ★★ same type
PGAM5 c.719+22C>T Benign ★★ same type
PGAM5 c.719+63A>G Benign ★★ same type
PGAM5 c.719+647C>T Benign ★★ same type
PGAM5 c.719+676C>G Benign ★★ same type
PGAM5 c.719+795T>C Benign ★★ 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/pgam5-p-pro55arg (accessed [today's date]).

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