Is ACE p.Pro504fs (c.1511del) pathogenic?

ACE p.Pro504fs (c.1511del) is classified Likely pathogenic in ACE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-30). Very rare (popmax 0.005%, amr); Associated with microvascular complications of diabetes, susceptibility to, 3.

What condition is associated with ACE p.Pro504fs (c.1511del)?

ACE p.Pro504fs (c.1511del) is associated with microvascular complications of diabetes, susceptibility to, 3, renal tubular dysgenesis of genetic origin, hemorrhage, intracerebral, susceptibility to (ClinVar).

How common is ACE p.Pro504fs (c.1511del) in the general population?

ACE p.Pro504fs (c.1511del) is very rare (popmax 0.005%, amr) (gnomAD).

ACE p.Pro504fs

c.1511del · rs1568038811 · VCV1723253

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

microvascular complications of diabetes, susceptibility to, 3

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 10 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.46	GERP -3.4, phastCons 0.002

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,008 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000558% 9/1,613,928 alleles · very rare exomes 9/1,461,710 · genomes 0/152,218 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,003
European (non-Finnish)	0.000509%	196,651

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.Pro504fs
Coding: c.1511del
MANE Select: NM_000789
dbSNP: rs1568038811
Type: Deletion
Location: chr17:63483482 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 504: the peptidase m2 1 domain

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

Disease context

microvascular complications of diabetes, susceptibility to, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: renal tubular dysgenesis of genetic origin hemorrhage, intracerebral, susceptibility to

Similar variants

ACE p.Pro504Ser Uncertain significance ★★ ⚠ same residue
ACE p.Arg8fs Pathogenic/Likely pathogenic ★★ same condition
ACE p.Arg862fs Likely pathogenic ★ same condition
ACE p.Lys722fs Likely pathogenic ★ same condition
ACE p.Ser1131fs 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

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-pro504fs (accessed [today's date]).

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