CSMD1 p.Pro428=
c.1284G>A · rs372720663 · VCV2658346
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.236%, nfe)
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 -15 | GERP -3.8 |
| Overall | ||
| CADD | 0.184 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.236%
European (non-Finnish) · 2,786/1,179,700 alleles
Filtering AF
0.229%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.226%
Overall
0.179%
2,886/1,613,268 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.236% | 423 |
| Remaining individualsnot grpmax-eligible | 0.0881% | 1,135 |
| African / African-American | 0.0387% | 2,586 |
| Finnishnot grpmax-eligible | 0.0125% | 8,000 |
| Admixed American | 0.01% | 10,001 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,799 |
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
- CSMD1
- Protein
- p.Pro428=
- Coding
- c.1284G>A
- MANE Select
- NM_033225
- dbSNP
- rs372720663
- Type
- single nucleotide variant
- Location
- chr8:3575005 (GRCh38)
- Gene constraint
- LOEUF 0.586 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Residue 428
- the cub 3 domain; a disulfide bond
Similar variants
- CSMD1 p.Ala1296Val Uncertain significance ★★ ⚠ same type
- CSMD1 p.Asp908Ala Uncertain significance ★★ ⚠ same type
- CSMD1 p.Asp927Asn Uncertain significance ★★ ⚠ same type
- CSMD1 p.Gln308Leu Uncertain significance ★★ ⚠ same type
- CSMD1 p.Glu1276Asp Uncertain significance ★★ ⚠ same type
- CSMD1 p.Gly3156Arg Uncertain significance ★★ ⚠ same type
- CSMD1 p.Ile1833Thr Uncertain significance ★★ ⚠ same type
- CSMD1 p.Lys1718Asn 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/csmd1-p-pro428 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown