Is ACE p.Arg482Cys (c.1444C>T) pathogenic?

ACE p.Arg482Cys (c.1444C>T) is classified Uncertain significance in ACE (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-01). AlphaMissense: likely benign (0.1159); Ultra-rare (popmax 0.0405%, nfe); Associated with renal tubular dysgenesis of genetic origin.

What condition is associated with ACE p.Arg482Cys (c.1444C>T)?

ACE p.Arg482Cys (c.1444C>T) is associated with renal tubular dysgenesis of genetic origin, microvascular complications of diabetes, susceptibility to, 3, renal tubular dysgenesis (ClinVar).

How common is ACE p.Arg482Cys (c.1444C>T) in the general population?

ACE p.Arg482Cys (c.1444C>T) is ultra-rare (popmax 0.0405%, nfe) (gnomAD).

What do computational predictors say about ACE p.Arg482Cys (c.1444C>T)?

AlphaMissense predicts likely benign (score 0.1159) — an in-silico prediction, not a clinical call.

ACE p.Arg482Cys

c.1444C>T · rs201540553 · VCV888832

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1159 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0405%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal tubular dysgenesis of genetic origin

Computational evidence

Protein change
AlphaMissense	0.1159	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -13.27	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	GERP -2.4
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0405% European (non-Finnish) · 478/1,180,012 alleles

Filtering AF 0.0375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0363%

Overall 0.0312% 504/1,614,080 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0405%	2,469
Remaining individualsnot grpmax-eligible	0.016%	6,250
Admixed American	0.00666%	15,005
Finnishnot grpmax-eligible	0.00625%	15,997
East Asian	0.00446%	22,435
South Asian	0.00439%	22,769
African / African-American	0.00267%	37,518

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.Arg482Cys
Coding: c.1444C>T
MANE Select: NM_000789
dbSNP: rs201540553
Type: single nucleotide variant
Location: chr17:63483130 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 482: a β-strand; the peptidase m2 1 domain

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

Disease context

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

Also linked: microvascular complications of diabetes, susceptibility to, 3 renal tubular dysgenesis hemorrhage, intracerebral, susceptibility to

Similar variants

ACE p.Arg482His Uncertain significance ★★ ⚠ same residue
ACE p.Arg482Pro Uncertain significance ★★ ⚠ same residue
ACE p.Arg482Leu Uncertain significance ★ ⚠ same residue
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

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-arg482cys (accessed [today's date]).

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