Is ACE p.Pro485Arg (c.1454C>G) pathogenic?

ACE p.Pro485Arg (c.1454C>G) is classified Uncertain significance in ACE (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.1007); Rare (popmax 0.102%, nfe); Associated with renal tubular dysgenesis.

What condition is associated with ACE p.Pro485Arg (c.1454C>G)?

ACE p.Pro485Arg (c.1454C>G) is associated with renal tubular dysgenesis (ClinVar).

How common is ACE p.Pro485Arg (c.1454C>G) in the general population?

ACE p.Pro485Arg (c.1454C>G) is rare (popmax 0.102%, nfe) (gnomAD).

What do computational predictors say about ACE p.Pro485Arg (c.1454C>G)?

AlphaMissense predicts likely benign (score 0.1007) — an in-silico prediction, not a clinical call.

ACE p.Pro485Arg

c.1454C>G · rs28730839 · VCV888833

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1007 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.102%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal tubular dysgenesis

Computational evidence

Protein change
AlphaMissense	0.1007	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -0.89, phastCons 0.26
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.102% European (non-Finnish) · 1,205/1,180,020 alleles

Filtering AF 0.0973% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0954%

Overall 0.0819% 1,322/1,614,086 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.102%	979
Admixed American	0.0916%	1,091
Remaining individualsnot grpmax-eligible	0.0768%	1,302
Middle Eastern	0.033%	3,030
African / African-American	0.0133%	7,505
Finnishnot grpmax-eligible	0.00313%	31,985

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.Pro485Arg
Coding: c.1454C>G
MANE Select: NM_000789
dbSNP: rs28730839
Type: single nucleotide variant
Location: chr17:63483140 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 485: an α-helix; the peptidase m2 1 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.Pro485Ala 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
ACE c.2739+5G>A Uncertain significance ★★ 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-pro485arg (accessed [today's date]).

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