Is ACE p.Leu573fs (c.1717del) pathogenic?

ACE p.Leu573fs (c.1717del) is classified Likely pathogenic in ACE (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-26). Very rare (popmax 8.48e-05%, nfe); Associated with ACE-related disorder.

What condition is associated with ACE p.Leu573fs (c.1717del)?

ACE p.Leu573fs (c.1717del) is associated with ACE-related disorder (ClinVar).

How common is ACE p.Leu573fs (c.1717del) in the general population?

ACE p.Leu573fs (c.1717del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

ACE p.Leu573fs

c.1717del · VCV4936520

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 8.48e-05%, nfe)

Conditions

ACE-related disorder

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 12 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP 1.7, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,714 alleles

Overall 6.86e-05% 1/1,458,010 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.Leu573fs
Coding: c.1717del
MANE Select: NM_000789
Type: Deletion
Location: chr17:63484337 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 573: an α-helix; the peptidase m2 1 domain

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

Disease context

ACE-related disorder

Similar variants

ACE p.Asp491fs Likely pathogenic ★ same condition
ACE c.2059-26_2059-4del Uncertain significance ★ same condition
ACE p.Leu20fs Conflicting classifications of pathogenicity ★ same condition
ACE c.3691+6del Likely benign same condition
ACE c.3691+9del Likely benign same condition
ACE p.Arg265Ter Pathogenic ★★ same condition
ACE p.Arg496Gln Likely pathogenic ★★ same condition
ACE p.Leu13_Leu14del Pathogenic/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/ace-p-leu573fs (accessed [today's date]).

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