Is ACE p.Arg8Leu (c.23G>T) pathogenic?

ACE p.Arg8Leu (c.23G>T) is classified Uncertain significance in ACE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-19). AlphaMissense: likely benign (0.1156); Absent from gnomAD v4.1; Associated with renal tubular dysgenesis of genetic origin.

What condition is associated with ACE p.Arg8Leu (c.23G>T)?

ACE p.Arg8Leu (c.23G>T) is associated with renal tubular dysgenesis of genetic origin, microvascular complications of diabetes, susceptibility to, 3, hemorrhage, intracerebral, susceptibility to (ClinVar).

How common is ACE p.Arg8Leu (c.23G>T) in the general population?

ACE p.Arg8Leu (c.23G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACE p.Arg8Leu (c.23G>T)?

AlphaMissense predicts likely benign (score 0.1156) — an in-silico prediction, not a clinical call.

ACE p.Arg8Leu

c.23G>T · VCV3582409

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1156 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,331,388)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal tubular dysgenesis of genetic origin

Computational evidence

Protein change
AlphaMissense	0.1156	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.42	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 -0.82	GERP -3.7
Regional constraint	o/e 1.04	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	0.641	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

No allele count reported in gnomAD v4.1 (AN 1,331,388). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACE
Protein: p.Arg8Leu
Coding: c.23G>T
MANE Select: NM_000789
Type: single nucleotide variant
Location: chr17:63477117 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB

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 hemorrhage, intracerebral, susceptibility to

Similar variants

ACE p.Arg8Trp Uncertain significance ★★ ⚠ same residue
ACE p.Arg8fs Pathogenic/Likely pathogenic ★★ same residue
ACE c.1342+1G>T 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.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-arg8leu (accessed [today's date]).

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