How is Dehydrated hereditary stomatocytosis inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PIEZO1 p.Pro2190=

Q: Is PIEZO1 p.Pro2190= (c.6570A>G) pathogenic?

PIEZO1 p.Pro2190= (c.6570A>G) is classified Benign/Likely benign in PIEZO1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 94.2%, mid) — too common for a highly-penetrant pathogenic allele; Associated with dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema.

Q: What condition is associated with PIEZO1 p.Pro2190= (c.6570A>G)?

PIEZO1 p.Pro2190= (c.6570A>G) is associated with dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, lymphatic malformation 6 (ClinVar).

Q: How common is PIEZO1 p.Pro2190= (c.6570A>G) in the general population?

PIEZO1 p.Pro2190= (c.6570A>G) is common (popmax 94.2%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6570A>G · rs6500491 · VCV440048

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 94.2%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.019	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -5
Overall
CADD	0.164	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 94.2% Middle Eastern · 5,646/5,992 alleles

Filtering AF 92.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 91.3%

Overall 89.8% 1,392,379/1,551,168 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	96.7%	1
Amishnot grpmax-eligible	94.4%	1
Middle Easterngrpmax	94.2%	1
Admixed American	90.8%	1
East Asian	90.8%	1
Remaining individualsnot grpmax-eligible	90%	1
European (non-Finnish)	89.9%	1
African / African-American	88.9%	1
Finnishnot grpmax-eligible	86.8%	1
South Asian	86.5%	1

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PIEZO1
Protein: p.Pro2190=
Coding: c.6570A>G
MANE Select: NM_001142864
dbSNP: rs6500491
Type: single nucleotide variant
Location: chr16:88717113 (GRCh38)
Gene constraint: LOEUF 1.17 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.74 · 6 PDB
Residue 2190: a UniProt-annotated variant site (found in er(a-b-) blood group phenotype); an α-helix

Full PIEZO1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lymphatic malformation 6

For Dehydrated hereditary stomatocytosis (Orphanet):

Inheritance: Autosomal dominant
Onset: Antenatal, Neonatal
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

PIEZO1 p.Ala2003Asp Likely pathogenic ★★ same condition
PIEZO1 p.Ala2020Thr Pathogenic/Likely pathogenic ★★ same condition
PIEZO1 p.Arg1164Ter Pathogenic/Likely pathogenic ★★ same condition
PIEZO1 p.Arg2456His Pathogenic ★★ same condition
PIEZO1 p.Gln1125Ter Pathogenic/Likely pathogenic ★★ same condition
PIEZO1 p.Gln422Ter Pathogenic ★★ same condition
PIEZO1 p.Glu1764Ter Likely pathogenic ★★ same condition
PIEZO1 p.Met2225Arg 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/piezo1-p-pro2190 (accessed [today's date]).

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