Is PGM1 p.Pro231Ser (c.691C>T) pathogenic?

PGM1 p.Pro231Ser (c.691C>T) is classified Uncertain significance in PGM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely pathogenic (0.6128); No allele count reported in gnomAD v4.1 (AN 1,612,482); Associated with Inborn genetic diseases.

What condition is associated with PGM1 p.Pro231Ser (c.691C>T)?

PGM1 p.Pro231Ser (c.691C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PGM1 p.Pro231Ser (c.691C>T) in the general population?

PGM1 p.Pro231Ser (c.691C>T) is no allele count reported in gnomAD v4.1 (AN 1,612,482) (gnomAD).

What do computational predictors say about PGM1 p.Pro231Ser (c.691C>T)?

AlphaMissense predicts likely pathogenic (score 0.6128) — an in-silico prediction, not a clinical call.

PGM1 p.Pro231Ser

c.691C>T · rs1649318233 · VCV2324788

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6128 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,482)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6128	likely pathogenic
REVEL	0.421	indeterminate
SaProt	LLR -11.46	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 41 kb · p 0.25 · regional, not allelic
Overall
CADD	25.2	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

No allele count reported in gnomAD v4.1 (AN 1,612,482). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PGM1
Protein: p.Pro231Ser
Coding: c.691C>T
MANE Select: NM_002633
dbSNP: rs1649318233
Type: single nucleotide variant
Location: chr1:63634837 (GRCh38)
Gene constraint: LOEUF 1.189 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 97.27 · 16 PDB
Residue 231: an α-helix

Full PGM1 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

PGM1 p.Ala245Val Uncertain significance ★★ ⚠ same condition
PGM1 p.Ala368Thr Uncertain significance ★★ ⚠ same condition
PGM1 p.Arg387His Uncertain significance ★★ ⚠ same condition
PGM1 p.Arg452His Uncertain significance ★★ ⚠ same condition
PGM1 p.Asn132Ser Uncertain significance ★★ ⚠ same condition
PGM1 p.Leu177Val Uncertain significance ★★ ⚠ same condition
PGM1 p.Ser372Phe Uncertain significance ★★ ⚠ same condition
PGM1 p.Ser483Gly 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/pgm1-p-pro231ser (accessed [today's date]).

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