Is ACE p.Gln59= (c.177G>A) pathogenic?

ACE p.Gln59= (c.177G>A) is classified Benign/Likely benign in ACE (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-06). Low-frequency (popmax 2.92%, eas); Associated with hemorrhage, intracerebral, susceptibility to.

What condition is associated with ACE p.Gln59= (c.177G>A)?

ACE p.Gln59= (c.177G>A) 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.Gln59= (c.177G>A) in the general population?

ACE p.Gln59= (c.177G>A) is low-frequency (popmax 2.92%, eas) (gnomAD).

ACE p.Gln59=

c.177G>A · rs147912715 · VCV324361

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.92%, eas)

Conditions

hemorrhage, intracerebral, susceptibility to

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.25	donor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4.8	GERP -2.2, phastCons 1
Overall
CADD	12.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.92% East Asian · 1,009/34,606 alleles

Filtering AF 2.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.71%

Overall 0.0744% 1,107/1,487,410 alleles · low-frequency exomes 1,021/1,336,306 · genomes 86/151,104 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	2.92%	34
Remaining individualsnot grpmax-eligible	0.0549%	1,823
South Asian	0.0419%	2,386
Admixed American	0.00629%	15,903
European (non-Finnish)	0.00268%	37,286
African / African-American	0.00145%	68,860

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.Gln59=
Coding: c.177G>A
MANE Select: NM_000789
dbSNP: rs147912715
Type: single nucleotide variant
Location: chr17:63477271 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 59: an α-helix; the peptidase m2 1 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-gln59 (accessed [today's date]).

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