Is ACE p.Val325= (c.975G>T) pathogenic?

ACE p.Val325= (c.975G>T) is classified Benign in ACE (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-21). Low-frequency (popmax 1.23%, nfe); Associated with renal tubular dysgenesis.

What condition is associated with ACE p.Val325= (c.975G>T)?

ACE p.Val325= (c.975G>T) is associated with renal tubular dysgenesis (ClinVar).

How common is ACE p.Val325= (c.975G>T) in the general population?

ACE p.Val325= (c.975G>T) is low-frequency (popmax 1.23%, nfe) (gnomAD).

ACE p.Val325=

c.975G>T · rs61738840 · VCV324373

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.23%, nfe)

Conditions

renal tubular dysgenesis

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 1.4	GERP -0.35, phastCons 1
Overall
CADD	8.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.23% European (non-Finnish) · 14,497/1,180,020 alleles

Filtering AF 1.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2%

Overall 1% 16,206/1,614,010 alleles · low-frequency exomes 15,032/1,461,692 · genomes 1,174/152,318 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.23%	81
Remaining individualsnot grpmax-eligible	0.856%	117
Ashkenazi Jewishnot grpmax-eligible	0.703%	142
Admixed American	0.67%	149
Middle Eastern	0.643%	155
Finnishnot grpmax-eligible	0.369%	271
African / African-American	0.225%	444
South Asian	0.132%	759

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.Val325=
Coding: c.975G>T
MANE Select: NM_000789
dbSNP: rs61738840
Type: single nucleotide variant
Location: chr17:63481595 (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 — 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-val325 (accessed [today's date]).

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