EFNB1 p.Ser281=
c.843G>A · rs143341175 · VCV737593
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, nfe)
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 -4.2 | GERP -4 |
| Overall | ||
| CADD | 1.375 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
European (non-Finnish) · 119/895,210 alleles
Filtering AF
0.0113%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0106%
Overall
0.0109%
132/1,210,269 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0133% | 7,523 |
| Remaining individualsnot grpmax-eligible | 0.0105% | 9,511 |
| South Asian | 0.00705% | 14,191 |
| African / African-American | 0.00348% | 28,724 |
| Admixed American | 0.00218% | 45,942 |
| Finnishnot grpmax-eligible | 0.00215% | 46,506 |
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.Ser281=
- Coding
- c.843G>A
- MANE Select
- NM_004429
- dbSNP
- rs143341175
- Type
- single nucleotide variant
- Location
- chrX:68840456 (GRCh38)
- Structure
- AlphaFold pLDDT 71.68 · 1 PDB
- Residue 281
- a modified residue (phosphoserine); the 'interaction with zhx2' region
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-ser281 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown