JAM2 p.Val41=
c.123A>G · rs8133602 · VCV1259131
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 29.5%, eas) — 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 | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP -1.7, phastCons 1 |
| Overall | ||
| CADD | 8.295 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
29.5%
East Asian · 13,159/44,632 alleles
Filtering AF
29.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 28.9%
Overall
9.2%
147,272/1,600,512 alleles · common
exomes 134,777/1,448,208 · genomes 12,495/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 29.5% | 3 |
| South Asian | 13.6% | 7 |
| Admixed American | 13.4% | 7 |
| Remaining individualsnot grpmax-eligible | 9.87% | 10 |
| Finnishnot grpmax-eligible | 8.99% | 11 |
| European (non-Finnish) | 8.27% | 12 |
| Middle Eastern | 8.08% | 12 |
| Ashkenazi Jewishnot grpmax-eligible | 7.09% | 14 |
| African / African-American | 3.65% | 27 |
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
- JAM2
- Protein
- p.Val41=
- Coding
- c.123A>G
- MANE Select
- NM_021219
- dbSNP
- rs8133602
- Type
- single nucleotide variant
- Location
- chr21:25683938 (GRCh38)
- Gene constraint
- LOEUF 0.93 · pLI 0.09 (gnomAD)
- Structure
- AlphaFold pLDDT 82.91
- Residue 41
- the ig-like v-type domain
Similar variants
- JAM2 p.Arg229Ter Pathogenic ★★ same type
- JAM2 c.68-96C>A Benign ★★ same type
- JAM2 c.697+127C>T Benign ★★ same type
- JAM2 c.698-21G>A Benign ★★ same type
- JAM2 c.805+30T>A Benign ★★ same type
- JAM2 c.806-21T>G Benign ★★ same type
- JAM2 c.821+181A>G Benign ★★ same type
- JAM2 c.865-102C>T Benign ★★ 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/jam2-p-val41 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown