CSMD3 p.Ile498=
c.1494C>T · rs61759498 · VCV776378
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 6.84%, afr) — 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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP -2.4, phastCons 1 |
| Overall | ||
| CADD | 10.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.84%
African / African-American · 4,839/70,732 alleles
Filtering AF
6.68%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.61%
Overall
0.386%
5,472/1,416,578 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.84% | 15 |
| Admixed American | 0.505% | 198 |
| Remaining individualsnot grpmax-eligible | 0.433% | 231 |
| Middle Eastern | 0.264% | 379 |
| South Asian | 0.0185% | 5,398 |
| European (non-Finnish) | 0.00598% | 16,709 |
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.Ile498=
- Coding
- c.1494C>T
- MANE Select
- NM_198123
- dbSNP
- rs61759498
- Type
- single nucleotide variant
- Location
- chr8:112947804 (GRCh38)
- Gene constraint
- LOEUF 0.464 · pLI 0.97 (gnomAD)
- Residue 498
- the sushi 2 domain; a disulfide bond
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-ile498 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown