Is ACE p.Ser1131fs (c.3391del) pathogenic?

ACE p.Ser1131fs (c.3391del) is classified Likely pathogenic in ACE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-17). Very rare (popmax 8.47e-05%, nfe); Associated with renal tubular dysgenesis of genetic origin.

What condition is associated with ACE p.Ser1131fs (c.3391del)?

ACE p.Ser1131fs (c.3391del) is associated with renal tubular dysgenesis of genetic origin, microvascular complications of diabetes, susceptibility to, 3, hemorrhage, intracerebral, susceptibility to (ClinVar).

How common is ACE p.Ser1131fs (c.3391del) in the general population?

ACE p.Ser1131fs (c.3391del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

ACE p.Ser1131fs

c.3391del · VCV3582573

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

renal tubular dysgenesis of genetic origin

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 23 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.023	GERP -2.3, phastCons 0.8

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,022 alleles

Overall 6.84e-05% 1/1,461,832 alleles · very rare

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: ACE
Protein: p.Ser1131fs
Coding: c.3391del
MANE Select: NM_000789
Type: Deletion
Location: chr17:63496404 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 1131: an α-helix; the peptidase m2 2 domain

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

Disease context

renal tubular dysgenesis of genetic origin — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: microvascular complications of diabetes, susceptibility to, 3 hemorrhage, intracerebral, susceptibility to

Similar variants

ACE p.Arg8fs Pathogenic/Likely pathogenic ★★ same condition
ACE p.Pro504fs Likely pathogenic ★★ same condition
ACE p.Arg862fs Likely pathogenic ★ same condition
ACE p.Lys722fs Likely pathogenic ★ same condition
ACE p.Val325fs Likely pathogenic ★ same condition
ACE c.1922-236_1922-219del Uncertain significance ★ same condition
ACE p.Gly1174fs Conflicting classifications of pathogenicity ★ same condition
ACE p.Leu13_Leu16del 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/ace-p-ser1131fs (accessed [today's date]).

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