Is ACE p.Ala80= (c.240A>G) pathogenic?

ACE p.Ala80= (c.240A>G) is classified Conflicting classifications of pathogenicity in ACE (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-14). Rare (popmax 0.683%, eas); Associated with renal tubular dysgenesis.

What condition is associated with ACE p.Ala80= (c.240A>G)?

ACE p.Ala80= (c.240A>G) is associated with renal tubular dysgenesis (ClinVar).

How common is ACE p.Ala80= (c.240A>G) in the general population?

ACE p.Ala80= (c.240A>G) is rare (popmax 0.683%, eas) (gnomAD).

ACE p.Ala80=

c.240A>G · rs370200820 · VCV890949

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.683%, eas)

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 0.73	GERP -4, phastCons 0.85
Overall
CADD	9.215	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.683% East Asian · 198/28,984 alleles

Filtering AF 0.605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.575%

Overall 0.0216% 286/1,322,254 alleles · rare exomes 230/1,175,828 · genomes 56/146,426 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.683%	146
South Asian	0.0515%	1,941
Finnishnot grpmax-eligible	0.0492%	2,031
Remaining individualsnot grpmax-eligible	0.0355%	2,818
Middle Eastern	0.0239%	4,178
Admixed American	0.00274%	36,468
European (non-Finnish)	0.00205%	48,680

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.Ala80=
Coding: c.240A>G
MANE Select: NM_000789
dbSNP: rs370200820
Type: single nucleotide variant
Location: chr17:63477334 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 80: 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-ala80 (accessed [today's date]).

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