Is PIEZO2 p.Pro2283Ser (c.6847C>T) pathogenic?

PIEZO2 p.Pro2283Ser (c.6847C>T) is classified Uncertain significance in PIEZO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-10). AlphaMissense: likely pathogenic (0.8664); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with PIEZO2 p.Pro2283Ser (c.6847C>T)?

PIEZO2 p.Pro2283Ser (c.6847C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PIEZO2 p.Pro2283Ser (c.6847C>T) in the general population?

PIEZO2 p.Pro2283Ser (c.6847C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about PIEZO2 p.Pro2283Ser (c.6847C>T)?

AlphaMissense predicts likely pathogenic (score 0.8664) — an in-silico prediction, not a clinical call.

PIEZO2 p.Pro2283Ser

c.6847C>T · VCV4627528

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8664 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8664	likely pathogenic
REVEL	0.469	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 99 kb · p 0.0051 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P2170S vs ClinVar P2283S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,010 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,613,590 alleles · very rare exomes 8/1,461,316 · genomes 0/152,274 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,010
European (non-Finnish)	0.000593%	168,568

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: PIEZO2
Protein: p.Pro2283Ser
Coding: c.6847C>T
MANE Select: NM_001378183
Type: single nucleotide variant
Location: chr18:10696520 (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-pro2283ser (accessed [today's date]).

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