Is ACE p.Asn194= (c.582C>T) pathogenic?

ACE p.Asn194= (c.582C>T) is classified Benign in ACE (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Common (popmax 35.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with renal tubular dysgenesis.

What condition is associated with ACE p.Asn194= (c.582C>T)?

ACE p.Asn194= (c.582C>T) is associated with renal tubular dysgenesis (ClinVar).

ACE p.Asn194=

Q: How common is ACE p.Asn194= (c.582C>T) in the general population?

ACE p.Asn194= (c.582C>T) is common (popmax 35.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.582C>T · rs4298 · VCV256809

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 35.6%, afr) — too common for a highly-penetrant pathogenic allele

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 -7.6	GERP -2.7
Overall
CADD	1.088	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 35.6% African / African-American · 26,674/75,018 alleles

Filtering AF 35.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 35.1%

Overall 8.17% 131,764/1,613,132 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	35.6%	3
Amishnot grpmax-eligible	16.4%	6
Middle Eastern	13.3%	8
Finnishnot grpmax-eligible	9.48%	11
Remaining individualsnot grpmax-eligible	8.96%	11
Ashkenazi Jewishnot grpmax-eligible	8.22%	12
European (non-Finnish)	6.95%	14
Admixed American	5.69%	18
South Asian	4.9%	20
East Asian	0.655%	153

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.Asn194=
Coding: c.582C>T
MANE Select: NM_000789
dbSNP: rs4298
Type: single nucleotide variant
Location: chr17:63479839 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 194: 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-asn194 (accessed [today's date]).

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