Is ACE p.Ile1267= (c.3801C>T) pathogenic?

ACE p.Ile1267= (c.3801C>T) is classified Benign/Likely benign in ACE (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-08). Rare (popmax 0.849%, mid); Associated with hemorrhage, intracerebral, susceptibility to.

What condition is associated with ACE p.Ile1267= (c.3801C>T)?

ACE p.Ile1267= (c.3801C>T) is associated with hemorrhage, intracerebral, susceptibility to, renal tubular dysgenesis of genetic origin, microvascular complications of diabetes, susceptibility to, 3 (ClinVar).

How common is ACE p.Ile1267= (c.3801C>T) in the general population?

ACE p.Ile1267= (c.3801C>T) is rare (popmax 0.849%, mid) (gnomAD).

ACE p.Ile1267=

c.3801C>T · rs144242912 · VCV324420

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.849%, mid)

Conditions

hemorrhage, intracerebral, susceptibility to

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 -0.55	GERP -3.4
Overall
CADD	5.136	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.849% Middle Eastern · 44/5,182 alleles

Filtering AF 0.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.58%

Overall 0.18% 2,846/1,579,314 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.849%	118
Remaining individualsnot grpmax-eligible	0.237%	422
Admixed American	0.219%	457
European (non-Finnish)	0.198%	506
South Asian	0.156%	639
Ashkenazi Jewishnot grpmax-eligible	0.118%	851
African / African-American	0.0536%	1,866
Finnishnot grpmax-eligible	0.034%	2,940

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.Ile1267=
Coding: c.3801C>T
MANE Select: NM_000789
dbSNP: rs144242912
Type: single nucleotide variant
Location: chr17:63497246 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB

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

Disease context

hemorrhage, intracerebral, susceptibility to — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: renal tubular dysgenesis of genetic origin microvascular complications of diabetes, susceptibility to, 3 renal tubular dysgenesis

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-ile1267 (accessed [today's date]).

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