Is ACE p.Asp820= (c.2460T>C) pathogenic?

ACE p.Asp820= (c.2460T>C) is classified Conflicting classifications of pathogenicity in ACE (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-11-17). Ultra-rare (popmax 0.033%, nfe); Associated with renal tubular dysgenesis.

What condition is associated with ACE p.Asp820= (c.2460T>C)?

ACE p.Asp820= (c.2460T>C) is associated with renal tubular dysgenesis (ClinVar).

How common is ACE p.Asp820= (c.2460T>C) in the general population?

ACE p.Asp820= (c.2460T>C) is ultra-rare (popmax 0.033%, nfe) (gnomAD).

ACE p.Asp820=

c.2460T>C · rs138035588 · VCV324395

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, 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 · T>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6	GERP -3.4
Overall
CADD	0.122	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% European (non-Finnish) · 390/1,180,034 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.0254% 410/1,613,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.033%	3,026
Remaining individualsnot grpmax-eligible	0.0256%	3,905
African / African-American	0.00534%	18,728

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.Asp820=
Coding: c.2460T>C
MANE Select: NM_000789
dbSNP: rs138035588
Type: single nucleotide variant
Location: chr17:63488951 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 820: the peptidase m2 2 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-asp820 (accessed [today's date]).

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