AVIL p.Gln444Ter
c.1330C>T · VCV4278441
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
nephrotic syndrome, type 21
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 12 of 20 |
| Splicing | ||
| SpliceAI | Δ0.74 | donor loss · deltas |
| Pangolin | Δ0.53 | loss · gain 0.34 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 55.0 | 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
- AVIL
- Protein
- p.Gln444Ter
- Coding
- c.1330C>T
- MANE Select
- NM_006576
- Type
- single nucleotide variant
- Location
- chr12:57807592 (GRCh38)
- Gene constraint
- LOEUF 0.81 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.82 · 1 PDB
- Residue 444
- the 'core' region
Similar variants
- AVIL p.Arg199Ter Likely pathogenic ★★ same condition
- AVIL p.Asn777Lys Uncertain significance ★★ ⚠ same condition
- AVIL p.Ile250Thr Uncertain significance ★★ ⚠ same condition
- AVIL p.Lys204Glu Benign/Likely benign ★★ same condition
- AVIL p.Arg135Gln Likely pathogenic ★ ⚠ same condition
- AVIL p.Glu584Ter Likely pathogenic ★ same condition
- AVIL p.Lys169Ter Likely pathogenic ★ same condition
- AVIL c.66+9G>A 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/avil-p-gln444ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown