JAM3 p.Asp224=
c.672C>T · rs201213184 · VCV2736028
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.014 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.22 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -9.4 | GERP -3.2 |
| Overall | ||
| CADD | 1.797 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
East Asian · 9/44,900 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00779%
Overall
0.00669%
108/1,613,984 alleles · ultra-rare
exomes 96/1,461,790 · genomes 12/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.02% | 4,989 |
| European (non-Finnish) | 0.0078% | 12,826 |
| South Asian | 0.00439% | 22,770 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,240 |
| African / African-American | 0.00133% | 74,918 |
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
- JAM3
- Protein
- p.Asp224=
- Coding
- c.672C>T
- MANE Select
- NM_032801
- dbSNP
- rs201213184
- Type
- single nucleotide variant
- Location
- chr11:134146005 (GRCh38)
- Gene constraint
- LOEUF 1.003 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 84.67
- Residue 224
- the ig-like c2-type domain
Similar variants
- JAM3 p.Asp224Tyr Uncertain significance ★ ⚠ same residue
- JAM3 c.612+1G>T Pathogenic ★★ same type
- JAM3 p.Ala2Ser Uncertain significance ★★ ⚠ same type
- JAM3 p.Arg107Trp Uncertain significance ★★ same type
- JAM3 p.Arg123Cys Uncertain significance ★★ ⚠ same type
- JAM3 p.Arg14Trp Uncertain significance ★★ ⚠ same type
- JAM3 p.Arg168Gln Uncertain significance ★★ ⚠ same type
- JAM3 p.Arg185Ile 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/jam3-p-asp224 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown