Is ACE p.Arg729= (c.2187G>T) pathogenic?

ACE p.Arg729= (c.2187G>T) is classified Benign/Likely benign in ACE (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-16). Low-frequency (popmax 2.09%, afr); Associated with renal tubular dysgenesis.

What condition is associated with ACE p.Arg729= (c.2187G>T)?

ACE p.Arg729= (c.2187G>T) is associated with renal tubular dysgenesis (ClinVar).

How common is ACE p.Arg729= (c.2187G>T) in the general population?

ACE p.Arg729= (c.2187G>T) is low-frequency (popmax 2.09%, afr) (gnomAD).

ACE p.Arg729=

c.2187G>T · rs35553988 · VCV790184

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.09%, afr)

Conditions

renal tubular dysgenesis

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 -0.026	GERP -0.78, phastCons 0.081
Overall
CADD	7.436	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.09% African / African-American · 1,571/75,056 alleles

Filtering AF 2.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.97%

Overall 0.112% 1,800/1,614,216 alleles · low-frequency exomes 871/1,461,876 · genomes 929/152,340 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.09%	48
Remaining individualsnot grpmax-eligible	0.173%	579
Middle Eastern	0.165%	606
Admixed American	0.16%	625
South Asian	0.00549%	18,215
European (non-Finnish)	0.000847%	118,005

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.Arg729=
Coding: c.2187G>T
MANE Select: NM_000789
dbSNP: rs35553988
Type: single nucleotide variant
Location: chr17:63486685 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 729: an α-helix; the peptidase m2 2 domain

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

Disease context

renal tubular dysgenesis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACE p.Arg729Gln Uncertain significance ★ ⚠ same residue
ACE p.Arg729Trp Uncertain significance ★ ⚠ same residue
ACE c.1709+5G>C Pathogenic/Likely pathogenic ★★ same condition
ACE c.3503+1G>C Likely pathogenic ★★ same condition
ACE p.Arg496Ter Pathogenic/Likely pathogenic ★★ same condition
ACE p.Arg508Ter Pathogenic ★★ same condition
ACE p.Arg791Ter Pathogenic ★★ same condition
ACE p.Tyr266Ter 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-arg729 (accessed [today's date]).

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