Is PIEZO2 p.Asp2004= (c.6012C>T) pathogenic?

PIEZO2 p.Asp2004= (c.6012C>T) is classified Benign/Likely benign in PIEZO2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-08). Common (popmax 5.39%, afr) — too common for a highly-penetrant pathogenic allele; Associated with arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome.

PIEZO2 p.Asp2004=

Q: What condition is associated with PIEZO2 p.Asp2004= (c.6012C>T)?

PIEZO2 p.Asp2004= (c.6012C>T) is associated with arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome, Gordon syndrome, Marden-Walker syndrome (ClinVar).

Q: How common is PIEZO2 p.Asp2004= (c.6012C>T) in the general population?

PIEZO2 p.Asp2004= (c.6012C>T) is common (popmax 5.39%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6012C>T · rs16975235 · VCV261518

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 5.39%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.6
Overall
CADD	0.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.39% African / African-American · 3,944/73,140 alleles

Filtering AF 5.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.19%

Overall 0.301% 4,630/1,536,402 alleles · common exomes 2,346/1,384,094 · genomes 2,284/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.39%	19
Middle Eastern	0.418%	239
Admixed American	0.326%	307
Remaining individualsnot grpmax-eligible	0.322%	311
South Asian	0.0893%	1,120
European (non-Finnish)	0.0195%	5,117
Ashkenazi Jewishnot grpmax-eligible	0.00698%	14,324
East Asian	0.00244%	40,900

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.Asp2004=
Coding: c.6012C>T
MANE Select: NM_001378183
dbSNP: rs16975235
Type: single nucleotide variant
Location: chr18:10704640 (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

Also linked: Gordon syndrome Marden-Walker syndrome arthrogryposis, distal, with impaired proprioception and touch

Similar variants

PIEZO2 p.Asp2004Asn Uncertain significance ★ same residue
PIEZO2 p.Asp2004Gly Uncertain significance ★ same residue
PIEZO2 c.1528-1G>A Likely pathogenic ★★ same condition
PIEZO2 c.4708+2T>G Likely pathogenic ★★ same condition
PIEZO2 c.5257-1G>A Pathogenic ★★ same condition
PIEZO2 p.Arg1600Ter Pathogenic/Likely pathogenic ★★ same condition
PIEZO2 p.Arg1743Ter Pathogenic/Likely pathogenic ★★ same condition
PIEZO2 p.Arg26Ter Likely 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-asp2004 (accessed [today's date]).

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