Is ACE p.Leu19= (c.57G>A) pathogenic?

ACE p.Leu19= (c.57G>A) is classified Likely benign in ACE (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-07-28). Very rare (popmax 0.00282%, nfe); Associated with ACE-related disorder.

What condition is associated with ACE p.Leu19= (c.57G>A)?

ACE p.Leu19= (c.57G>A) is associated with ACE-related disorder (ClinVar).

How common is ACE p.Leu19= (c.57G>A) in the general population?

ACE p.Leu19= (c.57G>A) is very rare (popmax 0.00282%, nfe) (gnomAD).

ACE p.Leu19=

c.57G>A · rs1384710532 · VCV3059091

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00282%, nfe)

Conditions

ACE-related disorder

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 0.9	GERP -0.29, phastCons 0.011
Overall
CADD	4.908	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00282% European (non-Finnish) · 31/1,100,534 alleles

Filtering AF 0.00202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00239% 31/1,294,594 alleles · very rare

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.Leu19=
Coding: c.57G>A
MANE Select: NM_000789
dbSNP: rs1384710532
Type: single nucleotide variant
Location: chr17:63477151 (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

ACE-related disorder

Similar variants

ACE p.Arg265Ter Pathogenic ★★ same condition
ACE p.Arg496Gln Likely pathogenic ★★ same condition
ACE p.Leu1024Phe Uncertain significance ★★ ⚠ same condition
ACE p.Lys571Asn Uncertain significance ★★ ⚠ same condition
ACE p.Val978Met Uncertain significance ★★ ⚠ same condition
ACE c.3503+1G>A Pathogenic ★ same condition
ACE p.Gln116Ter Likely pathogenic ★ same condition
ACE p.Gln63Ter 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-leu19 (accessed [today's date]).

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