AFF4 p.Arg1004Ter
c.3010C>T · VCV3765825
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
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 in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 18 of 21 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.6 | GERP 2.8, phastCons 1 |
| Overall | ||
| CADD | 38.0 | 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
- AFF4
- Protein
- p.Arg1004Ter
- Coding
- c.3010C>T
- MANE Select
- NM_014423
- Type
- single nucleotide variant
- Location
- chr5:132886399 (GRCh38)
- Gene constraint
- LOEUF 0.114 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.62 · 9 PDB
- Residue 1004
- an α-helix
Similar variants
- AFF4 p.Arg258Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- AFF4 p.Met260Val Likely pathogenic ★★ ⚠ same type
- AFF4 p.Pro253Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
- AFF4 p.Thr254Ser Pathogenic/Likely pathogenic ★★ ⚠ same type
- AFF4 c.1133+3A>G Uncertain significance ★★ same type
- AFF4 p.Ala114Thr Uncertain significance ★★ ⚠ same type
- AFF4 p.Ala114Val Uncertain significance ★★ ⚠ same type
- AFF4 p.Ala27Thr Uncertain significance ★★ ⚠ 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/aff4-p-arg1004ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown