Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 41.3%, amr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | acceptor -500 | deep intronic (-500 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.41 | GERP -2.1 |
| Non-coding constraint | Z 1.61 | 1 kb window · o/e 0.88 · regional · uncalibrated |
| Overall | ||
| CADD | 0.313 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
41.3%
Admixed American · 6,302/15,264 alleles
Filtering AF
40.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 40.1%
Overall
24.3%
37,019/152,052 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 41.3% | 2 |
| East Asian | 40.9% | 2 |
| South Asian | 35.4% | 3 |
| Amishnot grpmax-eligible | 33.4% | 3 |
| Finnishnot grpmax-eligible | 31.4% | 3 |
| European (non-Finnish) | 26.8% | 4 |
| Remaining individualsnot grpmax-eligible | 26.7% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 19% | 5 |
| Middle Eastern | 13.9% | 7 |
| African / African-American | 9.24% | 11 |
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
- EXT2
- Coding
- c.1663-500G>C
- MANE Select
- NM_207122
- dbSNP
- rs1113132
- Type
- single nucleotide variant
- Location
- chr11:44231853 (GRCh38)
- Gene constraint
- LOEUF 0.775 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 87.59 · 6 PDB
Similar variants
- EXT2 c.1079+1G>A Pathogenic ★★ same type
- EXT2 c.1079+1G>T Pathogenic ★★ same type
- EXT2 c.1173+1G>A Pathogenic ★★ same type
- EXT2 c.1662+1G>C Likely pathogenic ★★ same type
- EXT2 c.536+1G>A Pathogenic ★★ same type
- EXT2 c.626+1G>A Pathogenic ★★ same type
- EXT2 c.626+1G>C Pathogenic ★★ same type
- EXT2 c.626+1G>T Pathogenic/Likely pathogenic ★★ 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/ext2-c-1663-minus-500g-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown