RAD54L p.Arg2=
c.6G>A · rs2525626452 · VCV2593458
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.25 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 16.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000186%
3/1,614,160 alleles · ultra-rare
exomes 3/1,461,856 · genomes 0/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| European (non-Finnish) | 0.000169% | 590,016 |
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
- RAD54L
- Protein
- p.Arg2=
- Coding
- c.6G>A
- MANE Select
- NM_003579
- dbSNP
- rs2525626452
- Type
- single nucleotide variant
- Location
- chr1:46248514 (GRCh38)
- Gene constraint
- LOEUF 0.94 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.64 · 1 PDB
- Residue 2
- the 'disordered' region; the 'required for chromatin remodeling, strand pairing activities and coupling of atpase activity' region
Similar variants
- RAD54L p.Arg2Ser Uncertain significance ★ ⚠ same residue
- RAD54L p.Arg2Thr Uncertain significance ★ ⚠ same residue
- RAD54L p.Arg542Cys Likely pathogenic ★★ same type
- RAD54L p.Cys295Arg Uncertain significance ★★ ⚠ same type
- RAD54L p.Gly94Ala Uncertain significance ★★ ⚠ same type
- RAD54L p.Met590Thr Uncertain significance ★★ ⚠ same type
- RAD54L p.Phe733Val Uncertain significance ★★ ⚠ same type
- RAD54L p.Pro483Arg 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/rad54l-p-arg2 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown