INSRR p.Pro1263=
c.3789G>A · rs370144321 · VCV1675386
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.5 | GERP -5.2 |
| Overall | ||
| CADD | 0.052 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
Admixed American · 8/59,948 alleles
Filtering AF
0.00662%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00557%
Overall
0.00614%
99/1,613,514 alleles · ultra-rare
exomes 95/1,461,318 · genomes 4/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0133% | 7,493 |
| European (non-Finnish) | 0.00729% | 13,719 |
| African / African-American | 0.00534% | 18,730 |
| East Asian | 0.00223% | 44,868 |
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
- INSRR
- Protein
- p.Pro1263=
- Coding
- c.3789G>A
- MANE Select
- NM_014215
- dbSNP
- rs370144321
- Type
- single nucleotide variant
- Location
- chr1:156840978 (GRCh38)
- Gene constraint
- LOEUF 1.013 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.47 · 4 PDB
Similar variants
- INSRR p.Arg136Cys Uncertain significance ★★ ⚠ same type
- INSRR p.Ile1131Asn Uncertain significance ★★ ⚠ same type
- NTRK1 p.Ala40Glu Uncertain significance ★★ ⚠ same type
- INSRR c.1811-5C>T Benign ★★ same type
- INSRR p.Arg279Cys Likely benign ★★ ⚠ same type
- INSRR p.Arg554Cys Likely benign ★★ ⚠ same type
- INSRR p.Cys246Arg Likely benign ★★ same type
- INSRR p.Gln763= Benign ★★ 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/insrr-p-pro1263 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown