ACE p.Gln688Ter
c.2062C>T · VCV3391254
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
renal tubular dysgenesis of genetic origin
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 14 of 25 |
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.35 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -0.069 | GERP -2.6, phastCons 0.083 |
| Overall | ||
| CADD | 36.0 | 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
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ACE
- Protein
- p.Gln688Ter
- Coding
- c.2062C>T
- MANE Select
- NM_000789
- Type
- single nucleotide variant
- Location
- chr17:63486560 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.38 · 97 PDB
- Residue 688
- an α-helix; the peptidase m2 2 domain
Similar variants
- ACE c.1342+1G>T Likely pathogenic ★★ same condition
- ACE c.3503+1G>C Likely pathogenic ★★ same condition
- ACE c.945+2T>G Likely pathogenic ★★ same condition
- ACE p.Arg265Ter Pathogenic ★★ same condition
- ACE p.Arg508Ter Pathogenic ★★ same condition
- ACE p.Arg791Ter Pathogenic ★★ same condition
- ACE p.Gln396Ter Pathogenic/Likely pathogenic ★★ same condition
- ACE p.Met1Thr 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-gln688ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown