Is ACE p.Ala1163= (c.3489C>T) pathogenic?

ACE p.Ala1163= (c.3489C>T) is classified Benign/Likely benign in ACE (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-23). Rare (popmax 0.478%, afr); Associated with renal tubular dysgenesis of genetic origin.

What condition is associated with ACE p.Ala1163= (c.3489C>T)?

ACE p.Ala1163= (c.3489C>T) is associated with renal tubular dysgenesis of genetic origin, microvascular complications of diabetes, susceptibility to, 3, renal tubular dysgenesis (ClinVar).

How common is ACE p.Ala1163= (c.3489C>T) in the general population?

ACE p.Ala1163= (c.3489C>T) is rare (popmax 0.478%, afr) (gnomAD).

ACE p.Ala1163=

c.3489C>T · rs4979 · VCV889651

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.478%, afr)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7	GERP -3.7
Overall
CADD	2.305	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.478% African / African-American · 359/75,068 alleles

Filtering AF 0.437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.421%

Overall 0.0279% 451/1,614,100 alleles · rare exomes 250/1,461,748 · genomes 201/152,352 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.478%	209
Admixed American	0.055%	1,819
Middle Eastern	0.0495%	2,019
Remaining individualsnot grpmax-eligible	0.0352%	2,841
European (non-Finnish)	0.0028%	35,759
South Asian	0.0011%	91,070

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.Ala1163=
Coding: c.3489C>T
MANE Select: NM_000789
dbSNP: rs4979
Type: single nucleotide variant
Location: chr17:63496502 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 1163: 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 renal tubular dysgenesis hemorrhage, intracerebral, susceptibility to

Similar variants

ACE c.1342+1G>T Likely pathogenic ★★ same condition
ACE c.1709+5G>C Pathogenic/Likely pathogenic ★★ same condition
ACE c.3503+1G>C Likely pathogenic ★★ same condition
ACE c.945+2T>G Likely pathogenic ★★ same condition
ACE p.Arg265Ter Pathogenic ★★ same condition
ACE p.Arg496Ter Pathogenic/Likely pathogenic ★★ same condition
ACE p.Arg508Ter Pathogenic ★★ same condition
ACE p.Arg791Ter 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-ala1163 (accessed [today's date]).

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