Is ACE p.Gln47Arg (c.140A>G) pathogenic?

ACE p.Gln47Arg (c.140A>G) is classified Conflicting classifications of pathogenicity in ACE (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-06-03). AlphaMissense: likely benign (0.0619); Ultra-rare (popmax 0.0227%, eas); Associated with renal tubular dysgenesis.

What condition is associated with ACE p.Gln47Arg (c.140A>G)?

ACE p.Gln47Arg (c.140A>G) is associated with renal tubular dysgenesis (ClinVar).

How common is ACE p.Gln47Arg (c.140A>G) in the general population?

ACE p.Gln47Arg (c.140A>G) is ultra-rare (popmax 0.0227%, eas) (gnomAD).

What do computational predictors say about ACE p.Gln47Arg (c.140A>G)?

AlphaMissense predicts likely benign (score 0.0619) — an in-silico prediction, not a clinical call.

ACE p.Gln47Arg

c.140A>G · rs767353320 · VCV890393

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0619 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal tubular dysgenesis

Computational evidence

Protein change
AlphaMissense	0.0619	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -3.94	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 0.21	GERP -0.99
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	8.314	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 0.0227% East Asian · 8/35,284 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0082%

Overall 0.000799% 12/1,501,666 alleles · ultra-rare exomes 11/1,350,636 · genomes 1/151,030 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0227%	4,410
Remaining individualsnot grpmax-eligible	0.00348%	28,751
South Asian	0.00123%	80,974
European (non-Finnish)	8.86e-05%	1,128,462

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.Gln47Arg
Coding: c.140A>G
MANE Select: NM_000789
dbSNP: rs767353320
Type: single nucleotide variant
Location: chr17:63477234 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 47: 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 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
ACE p.Ala730Glu 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-gln47arg (accessed [today's date]).

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