AFF4 p.Pro467Arg
c.1400C>G · VCV3338238
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.444 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome
Computational evidence
| Protein change | ||
| AlphaMissense | 0.444 | ambiguous |
|---|---|---|
| REVEL | 0.625 | indeterminate |
| SaProt | LLR -7.25 | tolerated |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 5.6, phastCons 1 |
| Regional constraint | o/e 1.08 | unconstrained · MANE · 1,024 bp · p 0.75 · regional, not allelic |
| Overall | ||
| CADD | 28.5 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
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.Pro467Arg
- Coding
- c.1400C>G
- MANE Select
- NM_014423
- Type
- single nucleotide variant
- Location
- chr5:132897230 (GRCh38)
- Gene constraint
- LOEUF 0.114 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.62 · 9 PDB
- Residue 467
- the 'disordered' region
Similar variants
- AFF4 p.Pro467= Likely benign ★★ same residue
- AFF4 p.Arg258Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
- AFF4 p.Met260Val Likely pathogenic ★★ ⚠ same condition
- AFF4 p.Pro253Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
- AFF4 p.Thr254Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
- AFF4 c.1133+3A>G Uncertain significance ★★ same condition
- AFF4 p.Ala114Thr Uncertain significance ★★ ⚠ same condition
- AFF4 p.Ala114Val 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/aff4-p-pro467arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown