Is ACE p.Ile993= (c.2979C>T) pathogenic?

ACE p.Ile993= (c.2979C>T) is classified Benign/Likely benign in ACE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-04). Low-frequency (popmax 1.45%, afr); Associated with microvascular complications of diabetes, susceptibility to, 3.

What condition is associated with ACE p.Ile993= (c.2979C>T)?

ACE p.Ile993= (c.2979C>T) 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.Ile993= (c.2979C>T) in the general population?

ACE p.Ile993= (c.2979C>T) is low-frequency (popmax 1.45%, afr) (gnomAD).

ACE p.Ile993=

c.2979C>T · rs75067113 · VCV1650584

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.45%, afr)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.29	GERP -2.4, phastCons 0.88
Overall
CADD	5.329	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.45% African / African-American · 1,091/74,996 alleles

Filtering AF 1.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.35%

Overall 0.0732% 1,182/1,614,010 alleles · low-frequency exomes 545/1,461,858 · genomes 637/152,152 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.45%	69
Remaining individualsnot grpmax-eligible	0.0704%	1,421
Admixed American	0.06%	1,667
Middle Eastern	0.033%	3,027
South Asian	0.00439%	22,767
European (non-Finnish)	0.000424%	236,002

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.Ile993=
Coding: c.2979C>T
MANE Select: NM_000789
dbSNP: rs75067113
Type: single nucleotide variant
Location: chr17:63493502 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 993: an α-helix; the peptidase m2 2 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 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.Arg265Ter Pathogenic ★★ same condition
ACE p.Arg508Ter Pathogenic ★★ same condition
ACE p.Arg791Ter Pathogenic ★★ same condition
ACE p.Gln396Ter Pathogenic/Likely pathogenic ★★ same condition
ACE p.Met1Thr 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-ile993 (accessed [today's date]).

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