RECQL4 p.Pro222=
c.666T>C · rs752965461 · VCV1635119
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
Conditions
1
Baller-Gerold syndrome
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 · A>T here scores Δ0.89 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.6 | GERP -3 |
| Overall | ||
| CADD | 0.965 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/74,932 alleles
Overall
0.000124%
2/1,608,546 alleles · very rare
exomes 1/1,456,314 · genomes 1/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 74,932 |
| European (non-Finnish) | 8.48e-05% | 1,179,775 |
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
- RECQL4
- Protein
- p.Pro222=
- Coding
- c.666T>C
- MANE Select
- NM_004260
- dbSNP
- rs752965461
- Type
- single nucleotide variant
- Location
- chr8:144516453 (GRCh38)
- Gene constraint
- LOEUF 1.519 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.32 · 2 PDB
- Residue 222
- the 'disordered' region
Similar variants
- RECQL4 p.Pro222Arg Uncertain significance ★★ ⚠ same residue
- RECQL4 p.Pro222Leu Uncertain significance ★★ ⚠ same residue
- RECQL4 p.Pro222Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- RECQL4 c.1132-1G>A Likely pathogenic ★★ same condition
- RECQL4 c.1259-1G>A Pathogenic/Likely pathogenic ★★ same condition
- RECQL4 c.1391-1G>A Pathogenic ★★ same condition
- RECQL4 c.1704+1G>A Pathogenic/Likely pathogenic ★★ same condition
- RECQL4 c.1704+2T>G Likely pathogenic ★★ 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/recql4-p-pro222 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown