Is ACE p.Val325fs (c.973del) pathogenic?

ACE p.Val325fs (c.973del) is classified Likely pathogenic in ACE (ClinVar, Single submitter, 1 submitter). Ultra-rare (gnomAD MAF 7.136e-07); Associated with renal tubular dysgenesis of genetic origin.

What condition is associated with ACE p.Val325fs (c.973del)?

ACE p.Val325fs (c.973del) is associated with renal tubular dysgenesis of genetic origin (ClinVar).

How common is ACE p.Val325fs (c.973del) in the general population?

ACE p.Val325fs (c.973del) is ultra-rare (gnomAD MAF 7.136e-07) (gnomAD).

ACE p.Val325fs

c.973del · rs2510687443 · VCV2627964

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 7.136e-07)

Conditions

renal tubular dysgenesis of genetic origin

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP -0.56, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

Global frequency 7.14e-05% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: ACE
Protein: p.Val325fs
Coding: c.973del
MANE Select: NM_000789
dbSNP: rs2510687443
Type: Deletion
Location: chr17:63481591 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 325: 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 of genetic origin — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACE p.Arg8fs Pathogenic/Likely pathogenic ★★ same condition
ACE p.Pro504fs Likely pathogenic ★★ same condition
ACE p.Val325= Benign ★★ same residue
ACE p.Arg862fs Likely pathogenic ★ same condition
ACE p.Lys722fs Likely pathogenic ★ same condition
ACE p.Ser1131fs Likely pathogenic ★ same condition
ACE c.1922-236_1922-219del Uncertain significance ★ same condition
ACE p.Gly1174fs Conflicting classifications of pathogenicity ★ 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-val325fs (accessed [today's date]).

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