DEAF1 p.Arg224=
c.672G>C · VCV3905787
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 6.2e-05%)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2 | GERP -3.6 |
| Overall | ||
| CADD | 2.701 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.2e-05%
Overall
6.2e-05%
1/1,614,158 alleles · very rare
exomes 1/1,461,778 · genomes 0/152,380 · joint denominator
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
- DEAF1
- Protein
- p.Arg224=
- Coding
- c.672G>C
- MANE Select
- NM_021008
- Type
- single nucleotide variant
- Location
- chr11:686990 (GRCh38)
- Gene constraint
- LOEUF 1.18 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.62 · 3 PDB
- Residue 224
- the sand domain; a UniProt-annotated variant site (in vsvs; loss of deaf1-promoter repression; loss of transcriptional activation of eif4g3; loss of dna binding; decreased interaction with xrcc6)
Similar variants
- DEAF1 p.Arg224Pro Pathogenic/Likely pathogenic ★★ same residue
- DEAF1 p.Arg224Trp Pathogenic/Likely pathogenic ★★ same residue
- DEAF1 p.Arg224Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- DEAF1 p.Arg224Leu Uncertain significance ★ ⚠ same residue
- DEAF1 c.998-2A>G Likely pathogenic ★★ same type
- DEAF1 p.Arg226Trp Pathogenic/Likely pathogenic ★★ same type
- DEAF1 p.Arg246Thr Pathogenic/Likely pathogenic ★★ same type
- DEAF1 p.Arg261Ter Pathogenic/Likely 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/deaf1-p-arg224 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown