CSMD2 p.Phe258=
c.774C>T · rs201021410 · VCV2638637
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0541%, 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 3.4 | GERP -1.6, phastCons 1 |
| Overall | ||
| CADD | 9.422 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0541%
European (non-Finnish) · 638/1,180,046 alleles
Filtering AF
0.0506%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0492%
Overall
0.0455%
735/1,614,178 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0541% | 1,850 |
| Remaining individualsnot grpmax-eligible | 0.0416% | 2,404 |
| South Asian | 0.0406% | 2,462 |
| Middle Eastern | 0.033% | 3,031 |
| Finnishnot grpmax-eligible | 0.0172% | 5,818 |
| African / African-American | 0.016% | 6,256 |
| Admixed American | 0.0117% | 8,576 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,803 |
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
- CSMD2
- Protein
- p.Phe258=
- Coding
- c.774C>T
- MANE Select
- NM_001281956
- dbSNP
- rs201021410
- Type
- single nucleotide variant
- Location
- chr1:33918240 (GRCh38)
- Gene constraint
- LOEUF 0.364 · pLI 1.00 (gnomAD)
- Residue 258
- the cub 2 domain
Similar variants
- CSMD2 p.Pro1506= Likely benign ★★ same type
- CSMD2 p.Ser3015= Benign ★★ same type
- CSMD2 c.404+2T>A Uncertain significance ★ same type
- CSMD2 c.6344-398G>T Uncertain significance ★ same type
- CSMD2 c.6344-422A>G Uncertain significance ★ same type
- CSMD2 c.6344-423T>C Uncertain significance ★ same type
- CSMD2 c.6344-429G>A Uncertain significance ★ same type
- CSMD2 c.6344-435G>A 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/csmd2-p-phe258 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown