Is ACE p.Phe1129= (c.3387T>C) pathogenic?

ACE p.Phe1129= (c.3387T>C) is classified Benign/Likely benign in ACE (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 61.3%, sas) — too common for a highly-penetrant pathogenic allele; Associated with hemorrhage, intracerebral, susceptibility to.

What condition is associated with ACE p.Phe1129= (c.3387T>C)?

ACE p.Phe1129= (c.3387T>C) is associated with hemorrhage, intracerebral, susceptibility to, renal tubular dysgenesis of genetic origin, microvascular complications of diabetes, susceptibility to, 3 (ClinVar).

ACE p.Phe1129=

Q: How common is ACE p.Phe1129= (c.3387T>C) in the general population?

ACE p.Phe1129= (c.3387T>C) is common (popmax 61.3%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3387T>C · rs4362 · VCV256804

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 61.3%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

hemorrhage, intracerebral, susceptibility to

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.61 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.3	GERP -3.7
Overall
CADD	0.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 61.3% South Asian · 55,850/91,062 alleles

Filtering AF 60.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 60.7%

Overall 49.6% 800,917/1,613,968 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	61.3%	2
East Asian	58.6%	2
Admixed American	58.3%	2
African / African-American	57.6%	2
Remaining individualsnot grpmax-eligible	49.7%	2
European (non-Finnish)	48%	2
Finnishnot grpmax-eligible	45.8%	2
Amishnot grpmax-eligible	41.5%	2
Middle Eastern	41.1%	2
Ashkenazi Jewishnot grpmax-eligible	37.3%	3

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.Phe1129=
Coding: c.3387T>C
MANE Select: NM_000789
dbSNP: rs4362
Type: single nucleotide variant
Location: chr17:63496400 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 1129: an α-helix; the peptidase m2 2 domain

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-phe1129 (accessed [today's date]).

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