Is ACE p.Leu117= (c.349C>T) pathogenic?

ACE p.Leu117= (c.349C>T) is classified Conflicting classifications of pathogenicity in ACE (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-25). Ultra-rare (popmax 0.0112%, nfe); Associated with renal tubular dysgenesis.

What condition is associated with ACE p.Leu117= (c.349C>T)?

ACE p.Leu117= (c.349C>T) is associated with renal tubular dysgenesis (ClinVar).

How common is ACE p.Leu117= (c.349C>T) in the general population?

ACE p.Leu117= (c.349C>T) is ultra-rare (popmax 0.0112%, nfe) (gnomAD).

ACE p.Leu117=

c.349C>T · rs145692547 · VCV890952

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, nfe)

Conditions

renal tubular dysgenesis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.90 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.9	GERP 0.72, phastCons 1
Overall
CADD	9.528	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% European (non-Finnish) · 132/1,177,886 alleles

Filtering AF 0.00962% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00906%

Overall 0.00914% 147/1,608,520 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0191%	5,239
European (non-Finnish)grpmax	0.0112%	8,923
Ashkenazi Jewishnot grpmax-eligible	0.00679%	14,736
Remaining individualsnot grpmax-eligible	0.00161%	62,234

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu117=
Coding: c.349C>T
MANE Select: NM_000789
dbSNP: rs145692547
Type: single nucleotide variant
Location: chr17:63478030 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 117: 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-leu117 (accessed [today's date]).

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