EFNB1 p.Leu253=
c.759C>T · rs35567709 · VCV770019
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.75%, afr)
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 0.6 | GERP 0.042, phastCons 1 |
| Overall | ||
| CADD | 7.151 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.75%
African / African-American · 2,718/57,264 alleles
Filtering AF
4.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.54%
Overall
0.257%
3,116/1,210,384 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.75% | 21 |
| Admixed American | 0.381% | 262 |
| Remaining individualsnot grpmax-eligible | 0.372% | 269 |
| Middle Eastern | 0.115% | 871 |
| South Asian | 0.0141% | 7,104 |
| European (non-Finnish) | 0.00369% | 27,130 |
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
- EFNB1
- Protein
- p.Leu253=
- Coding
- c.759C>T
- MANE Select
- NM_004429
- dbSNP
- rs35567709
- Type
- single nucleotide variant
- Location
- chrX:68840372 (GRCh38)
- Structure
- AlphaFold pLDDT 71.68 · 1 PDB
Similar variants
- EFNB1 c.128+1G>C Likely pathogenic ★★ same type
- EFNB1 c.499+1G>A Pathogenic/Likely pathogenic ★★ same type
- EFNB1 p.Arg66Ter Pathogenic ★★ same type
- EFNB1 p.Gln175Ter Likely pathogenic ★★ same type
- EFNB1 p.Gln85Ter Pathogenic ★★ same type
- EFNB1 p.Gly10= Pathogenic ★★ same type
- EFNB1 p.Gly151Ser Pathogenic ★★ same type
- EFNB1 p.Met158Val 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/efnb1-p-leu253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown