Is ACE p.Ser486fs (c.1454dup) pathogenic?

ACE p.Ser486fs (c.1454dup) is classified Pathogenic in ACE (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-02). Very rare (popmax 0.00892%, eas); Associated with renal tubular dysgenesis.

What condition is associated with ACE p.Ser486fs (c.1454dup)?

ACE p.Ser486fs (c.1454dup) is associated with renal tubular dysgenesis (ClinVar).

How common is ACE p.Ser486fs (c.1454dup) in the general population?

ACE p.Ser486fs (c.1454dup) is very rare (popmax 0.00892%, eas) (gnomAD).

ACE p.Ser486fs

c.1454dup · rs758933315 · VCV1320127

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Conditions

renal tubular dysgenesis

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 9 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,818 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000744% 12/1,612,906 alleles · very rare exomes 12/1,461,516 · genomes 0/151,390 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,204
Admixed American	0.00167%	59,918
African / African-American	0.00134%	74,730
European (non-Finnish)	0.000509%	196,630

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.Ser486fs
Coding: c.1454dup
MANE Select: NM_000789
dbSNP: rs758933315
Type: Duplication
Location: chr17:63483133 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 486: 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 p.Ile462fs Pathogenic ★ same condition
ACE p.Ser486Phe Uncertain significance ★ ⚠ same residue
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.Ser5fs Pathogenic/Likely pathogenic ★★ 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-ser486fs (accessed [today's date]).

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