CROT c.116-1663C>A
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000272%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.172 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| Splice region | acceptor -1663 | deep intronic (-1663 nt into the intron) |
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.29 | GERP -0.31, phastCons 0.003 |
| Non-coding constraint | Z 0.48 | 1 kb window · o/e 0.96 · regional · uncalibrated |
| Overall | ||
| CADD | 5.84 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000272%
European (non-Finnish) · 3/1,101,056 alleles
Filtering AF
7.3e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2e-05%
Overall
0.000222%
3/1,349,004 alleles · very rare
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
- CROT
- Coding
- c.116-1663C>A
- MANE Select
- NM_021151
- Type
- single nucleotide variant
- Location
- chr7:87357543 (GRCh38)
- Gene constraint
- LOEUF 1.003 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.22
Similar variants
- CROT c.116-1631C>T Uncertain significance ★ same type
- CROT c.116-1651G>A Uncertain significance ★ same type
- CROT c.116-1686C>G Uncertain significance ★ same type
- CROT p.Ala104Val Uncertain significance ★ ⚠ same type
- CROT p.Arg12Gln Uncertain significance ★ ⚠ same type
- CROT p.Arg160Gln Uncertain significance ★ ⚠ same type
- CROT p.Arg389Gly Uncertain significance ★ ⚠ same type
- CROT p.Arg464Ser 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/crot-c-116-minus-1663c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown