Is PPP1CB p.Val249= (c.747G>T) pathogenic?

PPP1CB p.Val249= (c.747G>T) is classified Likely benign in PPP1CB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with PPP1CB p.Val249= (c.747G>T)?

PPP1CB p.Val249= (c.747G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is PPP1CB p.Val249= (c.747G>T) in the general population?

PPP1CB p.Val249= (c.747G>T) is absent from gnomAD v4.1 (gnomAD).

PPP1CB p.Val249=

c.747G>T · VCV3423735

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.37	GERP -1.8, phastCons 0.97
Overall
CADD	9.58	PHRED · no single calibrated threshold — expert panels disagree

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: PPP1CB
Protein: p.Val249=
Coding: c.747G>T
MANE Select: NM_002709
Type: single nucleotide variant
Location: chr2:28793865 (GRCh38)
Gene constraint: LOEUF 0.247 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.91

Full PPP1CB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PPP1CB p.Ala2Val Uncertain significance ★★ ⚠ same condition
PPP1CB p.Leu11Val Uncertain significance ★★ ⚠ same condition
PPP1CB p.Leu6Val Uncertain significance ★★ ⚠ same condition
PPP1CB p.Phe234Leu Uncertain significance ★★ ⚠ same condition
PPP1CB p.Ser99Cys Uncertain significance ★★ ⚠ same condition
PPP1CB p.Ala127= Likely benign ★★ same condition
PPP1CB p.Ala228= Likely benign ★★ same condition
PPP1CB p.Ala258= Likely benign ★★ 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/ppp1cb-p-val249 (accessed [today's date]).

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