NOTCH1 p.Arg56=
c.168A>G · rs779582015 · VCV2990380
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000173%, nfe)
Conditions
1
Adams-Oliver syndrome 5
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 -3.7 | GERP -2.4 |
| Overall | ||
| CADD | 6.805 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000173%
European (non-Finnish) · 2/1,156,076 alleles
Filtering AF
2.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000128%
2/1,567,202 alleles · very rare
exomes 2/1,415,016 · genomes 0/152,186 · 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
- NOTCH1
- Protein
- p.Arg56=
- Coding
- c.168A>G
- MANE Select
- NM_017617
- dbSNP
- rs779582015
- Type
- single nucleotide variant
- Location
- chr9:136523952 (GRCh38)
- Gene constraint
- LOEUF 0.217 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.74 · 29 PDB
- Residue 56
- the egf-like 1 domain
Similar variants
- NOTCH1 p.Arg56Ter Pathogenic ★★ same residue
- NOTCH1 p.Arg56Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- NOTCH1 c.1099+1G>T Pathogenic/Likely pathogenic ★★ same condition
- NOTCH1 c.3511-1G>A Likely pathogenic ★★ same condition
- NOTCH1 p.Arg1107Ter Pathogenic ★★ same condition
- NOTCH1 p.Arg448Ter Pathogenic ★★ same condition
- NOTCH1 p.Asp1517Asn Pathogenic/Likely pathogenic ★★ same condition
- NOTCH1 p.Cys1496Tyr Pathogenic/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/notch1-p-arg56 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown