Is PIEZO1 p.Pro47Arg (c.140C>G) pathogenic?

PIEZO1 p.Pro47Arg (c.140C>G) is classified Uncertain significance in PIEZO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-06). AlphaMissense: likely benign (0.3233); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PIEZO1 p.Pro47Arg (c.140C>G)?

PIEZO1 p.Pro47Arg (c.140C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PIEZO1 p.Pro47Arg (c.140C>G) in the general population?

PIEZO1 p.Pro47Arg (c.140C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PIEZO1 p.Pro47Arg (c.140C>G)?

AlphaMissense predicts likely benign (score 0.3233) — an in-silico prediction, not a clinical call.

PIEZO1 p.Pro47Arg

c.140C>G · rs772183217 · VCV2481217

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3233 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3233	likely benign
REVEL	0.521	indeterminate
SaProt	LLR -8.13	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 1.45	unconstrained · MANE · 69 kb · p 1.1e-155 · regional, not allelic
Overall
CADD	24.3	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: PIEZO1
Protein: p.Pro47Arg
Coding: c.140C>G
MANE Select: NM_001142864
dbSNP: rs772183217
Type: single nucleotide variant
Location: chr16:88749404 (GRCh38)
Gene constraint: LOEUF 1.17 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.74 · 6 PDB

Full PIEZO1 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

PIEZO1 p.Pro47= Likely benign ★★ same residue
PIEZO1 p.Ala1080Thr Uncertain significance ★★ ⚠ same condition
PIEZO1 p.Ala1109Val Uncertain significance ★★ ⚠ same condition
PIEZO1 p.Ala1447Val Uncertain significance ★★ ⚠ same condition
PIEZO1 p.Ala1474Thr Uncertain significance ★★ ⚠ same condition
PIEZO1 p.Ala1498Thr Uncertain significance ★★ ⚠ same condition
PIEZO1 p.Ala1685Val Uncertain significance ★★ ⚠ same condition
PIEZO1 p.Ala1956Thr 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/piezo1-p-pro47arg (accessed [today's date]).

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