Is ACE p.Pro340= (c.1020C>T) pathogenic?

ACE p.Pro340= (c.1020C>T) is classified Benign/Likely benign in ACE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-06-27). Rare (popmax 0.51%, eas); Associated with microvascular complications of diabetes, susceptibility to, 3.

What condition is associated with ACE p.Pro340= (c.1020C>T)?

ACE p.Pro340= (c.1020C>T) is associated with microvascular complications of diabetes, susceptibility to, 3, renal tubular dysgenesis of genetic origin, renal tubular dysgenesis (ClinVar).

How common is ACE p.Pro340= (c.1020C>T) in the general population?

ACE p.Pro340= (c.1020C>T) is rare (popmax 0.51%, eas) (gnomAD).

ACE p.Pro340=

c.1020C>T · rs3730026 · VCV891019

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.51%, eas)

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 -8.4	GERP -3.7
Overall
CADD	0.253	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.51% East Asian · 229/44,862 alleles

Filtering AF 0.456% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.435%

Overall 0.0154% 249/1,614,068 alleles · rare exomes 230/1,461,792 · genomes 19/152,276 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.51%	196
Remaining individualsnot grpmax-eligible	0.0096%	10,418
South Asian	0.00549%	18,215
African / African-American	0.00533%	18,762
European (non-Finnish)	0.000424%	236,003

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.Pro340=
Coding: c.1020C>T
MANE Select: NM_000789
dbSNP: rs3730026
Type: single nucleotide variant
Location: chr17:63481640 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 340: an α-helix; the peptidase m2 1 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 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-pro340 (accessed [today's date]).

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