CSMD1 p.Pro554=
c.1662G>A · rs182017822 · VCV774668
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.791%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.05 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP 0.22, phastCons 1 |
| Overall | ||
| CADD | 16.18 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.791%
European (non-Finnish) · 9,326/1,178,768 alleles
Filtering AF
0.778%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.772%
Overall
0.639%
10,288/1,611,056 alleles · rare
exomes 9,645/1,458,786 · genomes 643/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.791% | 126 |
| Remaining individualsnot grpmax-eligible | 0.628% | 159 |
| Admixed American | 0.478% | 209 |
| Middle Eastern | 0.116% | 865 |
| African / African-American | 0.109% | 914 |
| South Asian | 0.0998% | 1,002 |
| Finnishnot grpmax-eligible | 0.0845% | 1,183 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0813% | 1,230 |
| East Asian | 0.0625% | 1,599 |
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.Pro554=
- Coding
- c.1662G>A
- MANE Select
- NM_033225
- dbSNP
- rs182017822
- Type
- single nucleotide variant
- Location
- chr8:3409505 (GRCh38)
- Gene constraint
- LOEUF 0.586 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Residue 554
- the sushi 3 domain
Similar variants
- CSMD1 p.Pro554Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown