Is PIEZO2 p.Phe495Cys (c.1484T>G) pathogenic?

PIEZO2 p.Phe495Cys (c.1484T>G) is classified Likely pathogenic in PIEZO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-15). AlphaMissense: likely pathogenic (0.8682); Absent from gnomAD v4.1; Associated with Gordon syndrome.

What condition is associated with PIEZO2 p.Phe495Cys (c.1484T>G)?

PIEZO2 p.Phe495Cys (c.1484T>G) is associated with Gordon syndrome (ClinVar).

How common is PIEZO2 p.Phe495Cys (c.1484T>G) in the general population?

PIEZO2 p.Phe495Cys (c.1484T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PIEZO2 p.Phe495Cys (c.1484T>G)?

AlphaMissense predicts likely pathogenic (score 0.8682) — an in-silico prediction, not a clinical call.

PIEZO2 p.Phe495Cys

c.1484T>G · rs2510766806 · VCV3236261

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8682 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Gordon syndrome

Computational evidence

Protein change
AlphaMissense	0.8682	likely pathogenic ✓ concordant with ClinVar
REVEL	0.784	moderately 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	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 351 kb · p 0.0097 · regional, not allelic
Overall
CADD	27.6	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.Phe495Cys
Coding: c.1484T>G
MANE Select: NM_001378183
dbSNP: rs2510766806
Type: single nucleotide variant
Location: chr18:10797417 (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

Gordon syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PIEZO2 c.4708+2T>G Likely pathogenic ★★ same condition
PIEZO2 p.Arg2799Cys Pathogenic/Likely pathogenic ★★ same condition
PIEZO2 p.Arg2799Gly Pathogenic/Likely pathogenic ★★ same condition
PIEZO2 p.Arg2799His Pathogenic ★★ same condition
PIEZO2 p.Glu2603Ter Pathogenic ★★ same condition
PIEZO2 p.Asp817His Uncertain significance ★★ same condition
PIEZO2 p.Glu909Gln Uncertain significance ★★ ⚠ same condition
PIEZO2 p.Gly29Val 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-phe495cys (accessed [today's date]).

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