CSMD3 p.Thr1246=
c.3738G>A · rs1395803496 · VCV749610
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00671%, eas)
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 1.8 | GERP -1.3, phastCons 1 |
| Overall | ||
| CADD | 11.15 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00671%
East Asian · 3/44,710 alleles
Filtering AF
0.00178%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000893%
Overall
0.000808%
13/1,609,456 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00671% | 14,903 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,298 |
| African / African-American | 0.00134% | 74,702 |
| European (non-Finnish) | 0.00068% | 147,107 |
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
- CSMD3
- Protein
- p.Thr1246=
- Coding
- c.3738G>A
- MANE Select
- NM_198123
- dbSNP
- rs1395803496
- Type
- single nucleotide variant
- Location
- chr8:112587213 (GRCh38)
- Gene constraint
- LOEUF 0.464 · pLI 0.97 (gnomAD)
- Residue 1246
- a disulfide bond; the cub 7 domain
Similar variants
- CSMD3 p.Glu2761Val Uncertain significance ★★ same type
- CSMD3 p.Leu3027Phe Uncertain significance ★★ same type
- CSMD3 c.4896-3C>T Benign ★★ same type
- CSMD3 p.Arg1020His Benign ★★ same type
- CSMD3 p.Arg1228Gln Likely benign ★★ same type
- CSMD3 p.Arg687= Benign/Likely benign ★★ same type
- CSMD3 p.Asp1025= Benign ★★ same type
- CSMD3 p.Asp1473= 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/csmd3-p-thr1246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown