EPHB6 p.Thr246Met
c.737C>T · rs61732977 · VCV2560070
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.054%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.732 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6 | GERP 0.89, phastCons 1 |
| Overall | ||
| CADD | 27.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.054%
European (non-Finnish) · 637/1,179,956 alleles
Filtering AF
0.0505%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0491%
Overall
0.0426%
687/1,613,378 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.054% | 1,852 |
| East Asian | 0.0423% | 2,362 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,464 |
| South Asian | 0.00769% | 13,011 |
| Admixed American | 0.00666% | 15,006 |
| African / African-American | 0.00666% | 15,007 |
| Finnishnot grpmax-eligible | 0.00158% | 63,332 |
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
- EPHB6
- Protein
- p.Thr246Met
- Coding
- c.737C>T
- MANE Select
- NM_004445
- dbSNP
- rs61732977
- Type
- single nucleotide variant
- Location
- chr7:142864537 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.36 · 1 PDB
Similar variants
- EPHB6 p.Thr246Lys Uncertain significance ★ same residue
- TRPV6 p.Arg390Cys Uncertain significance ★★ ⚠ same type
- EPHB6 p.Arg905Gln Likely benign ★★ same type
- EPHB6 p.Ala341Pro Uncertain significance ★ same type
- EPHB6 p.Ala341Ser Uncertain significance ★ same type
- EPHB6 p.Ala341Thr Uncertain significance ★ same type
- EPHB6 p.Ala453Ser Uncertain significance ★ same type
- EPHB6 p.Ala567Val 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/ephb6-p-thr246met (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown