CSMD3 p.Ser2133=
c.6399C>T · rs141293957 · VCV3048334
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.178%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.36 | donor loss, 43 bp away · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.25 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 6.7 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 9.242 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.178%
European (non-Finnish) · 2,094/1,178,914 alleles
Filtering AF
0.171%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.169%
Overall
0.145%
2,338/1,612,842 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.178% | 563 |
| Finnishnot grpmax-eligible | 0.162% | 616 |
| Remaining individualsnot grpmax-eligible | 0.112% | 892 |
| South Asian | 0.045% | 2,221 |
| African / African-American | 0.024% | 4,167 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0169% | 5,918 |
| Admixed American | 0.01% | 10,002 |
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.Ser2133=
- Coding
- c.6399C>T
- MANE Select
- NM_198123
- dbSNP
- rs141293957
- Type
- single nucleotide variant
- Location
- chr8:112346140 (GRCh38)
- Gene constraint
- LOEUF 0.464 · pLI 0.97 (gnomAD)
- Residue 2133
- a disulfide bond; the cub 12 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-ser2133 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown