RTCB p.Ile248=
c.744C>T · VCV3948215
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0154%, sas)
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 -1.1 | GERP -3.5 |
| Overall | ||
| CADD | 8.664 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0154%
South Asian · 14/91,070 alleles
Filtering AF
0.0092%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00735%
Overall
0.00136%
22/1,614,064 alleles · ultra-rare
exomes 22/1,461,858 · genomes 0/152,206 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0154% | 6,505 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,833 |
| Finnishnot grpmax-eligible | 0.00156% | 64,002 |
| European (non-Finnish) | 0.000339% | 295,008 |
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
- RTCB
- Protein
- p.Ile248=
- Coding
- c.744C>T
- MANE Select
- NM_014306
- Type
- single nucleotide variant
- Location
- chr22:32398011 (GRCh38)
- Gene constraint
- LOEUF 0.622 · pLI 0.17 (gnomAD)
- Structure
- AlphaFold pLDDT 95.66 · 5 PDB
Similar variants
- RTCB p.Ala276= Benign ★★ same type
- RTCB p.Val347= Benign ★★ same type
- RTCB p.Ala101Thr Uncertain significance ★ ⚠ same type
- RTCB p.Ala211Val Uncertain significance ★ ⚠ same type
- RTCB p.Ala242Ser Uncertain significance ★ ⚠ same type
- RTCB p.Ala294Val Uncertain significance ★ ⚠ same type
- RTCB p.Ala296Thr Uncertain significance ★ ⚠ same type
- RTCB p.Ala333Ser 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/rtcb-p-ile248 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown