Is PIEZO2 p.Pro92fs (c.273_279del) pathogenic?

PIEZO2 p.Pro92fs (c.273279del) is classified Likely pathogenic in PIEZO2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-22). No gnomAD frequency available for this variant; Associated with arthrogryposis, distal, with impaired proprioception and touch.

What condition is associated with PIEZO2 p.Pro92fs (c.273_279del)?

PIEZO2 p.Pro92fs (c.273_279del) is associated with arthrogryposis, distal, with impaired proprioception and touch (ClinVar).

How common is PIEZO2 p.Pro92fs (c.273_279del) in the general population?

PIEZO2 p.Pro92fs (c.273_279del) is no gnomAD frequency available for this variant (gnomAD).

PIEZO2 p.Pro92fs

c.273_279del · rs2145486698 · VCV1339520

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

arthrogryposis, distal, with impaired proprioception and touch

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 56
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: PIEZO2
Protein: p.Pro92fs
Coding: c.273_279del
MANE Select: NM_001378183
dbSNP: rs2145486698
Type: Deletion
Location: chr18:10979542 (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

arthrogryposis, distal, with impaired proprioception and touch — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PIEZO2 p.Lys1592fs Pathogenic/Likely pathogenic ★★ same condition
PIEZO2 c.2170-18del Benign/Likely benign ★★ same condition
PIEZO2 c.2170-19_2170-18del Benign ★★ same condition
PIEZO2 c.2492+48del Benign ★★ same condition
PIEZO2 c.7953-9del Benign ★★ same condition
PIEZO2 c.6828-8_6829del Pathogenic ★ same condition
PIEZO2 p.Ala349fs Likely pathogenic ★ same condition
PIEZO2 p.Ala899fs Pathogenic ★ 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-pro92fs (accessed [today's date]).

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