Is ACE p.Pro1180Val (c.3538_3539delinsGT) pathogenic?

ACE p.Pro1180Val (c.35383539delinsGT) is classified Uncertain significance in ACE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-10-24). No gnomAD frequency available for this variant; Associated with renal tubular dysgenesis of genetic origin.

What condition is associated with ACE p.Pro1180Val (c.3538_3539delinsGT)?

ACE p.Pro1180Val (c.3538_3539delinsGT) 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.Pro1180Val (c.3538_3539delinsGT) in the general population?

ACE p.Pro1180Val (c.3538_3539delinsGT) is no gnomAD frequency available for this variant (gnomAD).

ACE p.Pro1180Val

c.3538_3539delinsGT · rs1568048955 · VCV591822

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

renal tubular dysgenesis of genetic origin

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACE
Protein: p.Pro1180Val
Coding: c.3538_3539delinsGT
MANE Select: NM_000789
dbSNP: rs1568048955
Type: Indel
Location: chr17:63496832 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 1180: 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.Pro1180= Likely benign ★★ same residue
ACE p.Ala596Phe Uncertain significance ★ same condition
ACE p.Pro1180Leu Uncertain significance ★ ⚠ same residue
ACE c.1342+1G>T Likely pathogenic ★★ same condition
ACE c.3503+1G>C Likely pathogenic ★★ same condition
ACE c.945+2T>G Likely pathogenic ★★ same condition
ACE p.Arg149fs Pathogenic ★★ same condition
ACE p.Arg265Ter 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-pro1180val (accessed [today's date]).

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