CSMD1 p.Ser194=
c.582G>A · rs377756447 · VCV741183
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0992%, mid)
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 -1.9 | GERP -4.4 |
| Overall | ||
| CADD | 2.961 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0992%
Middle Eastern · 6/6,046 alleles
Filtering AF
0.0432%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0295%
Overall
0.00979%
158/1,613,682 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0992% | 1,008 |
| Admixed American | 0.035% | 2,856 |
| South Asian | 0.0285% | 3,503 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,939 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0135% | 7,399 |
| European (non-Finnish) | 0.00746% | 13,407 |
| African / African-American | 0.00401% | 24,966 |
| East Asian | 0.00223% | 44,874 |
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.Ser194=
- Coding
- c.582G>A
- MANE Select
- NM_033225
- dbSNP
- rs377756447
- Type
- single nucleotide variant
- Location
- chr8:4031933 (GRCh38)
- Gene constraint
- LOEUF 0.586 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Residue 194
- the sushi 1 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-ser194 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown