Is PIEZO1 p.Leu1026Val (c.3076C>G) pathogenic?

PIEZO1 p.Leu1026Val (c.3076C>G) is classified Uncertain significance in PIEZO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). AlphaMissense: likely benign (0.1301); Very rare (popmax 0.00616%, eas); Associated with Inborn genetic diseases.

What condition is associated with PIEZO1 p.Leu1026Val (c.3076C>G)?

PIEZO1 p.Leu1026Val (c.3076C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PIEZO1 p.Leu1026Val (c.3076C>G) in the general population?

PIEZO1 p.Leu1026Val (c.3076C>G) is very rare (popmax 0.00616%, eas) (gnomAD).

What do computational predictors say about PIEZO1 p.Leu1026Val (c.3076C>G)?

AlphaMissense predicts likely benign (score 0.1301) — an in-silico prediction, not a clinical call.

PIEZO1 p.Leu1026Val

c.3076C>G · VCV3932077

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1301 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00616%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1301	likely benign
REVEL	0.438	indeterminate
SaProt	LLR -7.91	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.5	GERP -0.1, phastCons 1
Regional constraint	o/e 1.45	unconstrained · MANE · 69 kb · p 1.1e-155 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00616% East Asian · 2/32,470 alleles

Filtering AF 0.00102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000381%

Overall 0.000418% 6/1,434,494 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00616%	16,235
Admixed American	0.00229%	43,708
African / African-American	0.00161%	62,198
South Asian	0.00122%	81,678
European (non-Finnish)	9.25e-05%	1,080,564

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.Leu1026Val
Coding: c.3076C>G
MANE Select: NM_001142864
Type: single nucleotide variant
Location: chr16:88731826 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-leu1026val (accessed [today's date]).

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