Is PIEZO2 p.Pro265Ser (c.793C>T) pathogenic?

PIEZO2 p.Pro265Ser (c.793C>T) is classified Uncertain significance in PIEZO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-31). AlphaMissense: likely benign (0.1998); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PIEZO2 p.Pro265Ser (c.793C>T)?

PIEZO2 p.Pro265Ser (c.793C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PIEZO2 p.Pro265Ser (c.793C>T) in the general population?

PIEZO2 p.Pro265Ser (c.793C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PIEZO2 p.Pro265Ser (c.793C>T)?

AlphaMissense predicts likely benign (score 0.1998) — an in-silico prediction, not a clinical call.

PIEZO2 p.Pro265Ser

c.793C>T · VCV3888732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1998	likely benign
REVEL	0.412	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 351 kb · p 0.0097 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: PIEZO2
Protein: p.Pro265Ser
Coding: c.793C>T
MANE Select: NM_001378183
Type: single nucleotide variant
Location: chr18:10855477 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)

Full PIEZO2 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

PIEZO2 p.Ala1280Thr Uncertain significance ★★ same condition
PIEZO2 p.Ala1917Val Uncertain significance ★★ ⚠ same condition
PIEZO2 p.Ala2191Thr Uncertain significance ★★ ⚠ same condition
PIEZO2 p.Ala2329Gly Uncertain significance ★★ same condition
PIEZO2 p.Arg1743Gln Uncertain significance ★★ ⚠ same condition
PIEZO2 p.Arg1748Ser Uncertain significance ★★ same condition
PIEZO2 p.Arg202Leu Uncertain significance ★★ same condition
PIEZO2 p.Arg2211Cys 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/piezo2-p-pro265ser (accessed [today's date]).

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