Is ACE p.Tyr892fs (c.2673_2674dup) pathogenic?

ACE p.Tyr892fs (c.26732674dup) is classified Pathogenic in ACE (ClinVar, Single submitter, 3 submitters; last evaluated 2023-10-13). Very rare (popmax 0.00133%, afr).

How common is ACE p.Tyr892fs (c.2673_2674dup) in the general population?

ACE p.Tyr892fs (c.2673_2674dup) is very rare (popmax 0.00133%, afr) (gnomAD).

ACE p.Tyr892fs

c.2673_2674dup · rs2030333357 · VCV1285224

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 18 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.3	GERP 1.8, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,054 alleles

Overall 0.000657% 1/152,280 alleles · very rare

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.Tyr892fs
Coding: c.2673_2674dup
MANE Select: NM_000789
dbSNP: rs2030333357
Type: Duplication
Location: chr17:63490983 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.38 · 97 PDB
Residue 892: an α-helix; the peptidase m2 2 domain

Full ACE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACE p.Tyr892Cys Uncertain significance ★ ⚠ same residue
ACE p.Ala279fs Pathogenic ★ same type
ACE p.Arg409fs Likely pathogenic ★ same type
ACE p.Asp823fs Likely pathogenic ★ same type
ACE p.Ile462fs Pathogenic ★ same type
ACE p.Leu18fs Likely pathogenic ★ same type
ACE p.Phe479fs Likely pathogenic ★ same type
ACE p.Ser486fs Pathogenic ★ same type

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-tyr892fs (accessed [today's date]).

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