Is PIEZO2 p.Ser2852Pro (c.8554T>C) pathogenic?

PIEZO2 p.Ser2852Pro (c.8554T>C) is classified Pathogenic in PIEZO2 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2014-06-04). AlphaMissense: likely pathogenic (0.9993); Absent from gnomAD v4.1; Associated with arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome.

What condition is associated with PIEZO2 p.Ser2852Pro (c.8554T>C)?

PIEZO2 p.Ser2852Pro (c.8554T>C) is associated with arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome (ClinVar).

How common is PIEZO2 p.Ser2852Pro (c.8554T>C) in the general population?

PIEZO2 p.Ser2852Pro (c.8554T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PIEZO2 p.Ser2852Pro (c.8554T>C)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

PIEZO2 p.Ser2852Pro

c.8554T>C · rs587777454 · VCV137634

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic ✓ concordant with ClinVar · top 1% in PIEZO2
REVEL	0.948	strongly pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 11 kb · p 0.096 · regional, not allelic
Overall
CADD	26.3	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 S2739P vs ClinVar S2852P) — verify the residue.

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.Ser2852Pro
Coding: c.8554T>C
MANE Select: NM_001378183
dbSNP: rs587777454
Type: single nucleotide variant
Location: chr18:10671571 (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- oculomotor limitation-electroretinal anomalies syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PIEZO2 p.Ser2852Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PIEZO2 c.4708+2T>G Likely pathogenic ★★ same condition
PIEZO2 p.Arg2799Gly Pathogenic/Likely pathogenic ★★ same condition
PIEZO2 p.Arg2799His Pathogenic ★★ same condition
PIEZO2 p.Met1023Ile Pathogenic/Likely pathogenic ★★ same condition
PIEZO2 p.Met712Val Pathogenic/Likely pathogenic ★★ same condition
PIEZO2 p.Arg2495Gln Uncertain significance ★★ same condition
PIEZO2 p.Asp817His 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-ser2852pro (accessed [today's date]).

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