CLMN p.Ala223=
c.669G>A · rs150700470 · VCV2644494
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0209%, afr)
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 -4.9 | GERP -5.3 |
| Overall | ||
| CADD | 0.925 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0209%
African / African-American · 15/71,852 alleles
Filtering AF
0.0128%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0104%
Overall
0.0026%
41/1,579,458 alleles · ultra-rare
exomes 26/1,427,214 · genomes 15/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0209% | 4,790 |
| Middle Eastern | 0.0169% | 5,910 |
| Admixed American | 0.00785% | 12,735 |
| European (non-Finnish) | 0.00171% | 58,399 |
| Remaining individualsnot grpmax-eligible | 0.00164% | 60,934 |
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
- CLMN
- Protein
- p.Ala223=
- Coding
- c.669G>A
- MANE Select
- NM_024734
- dbSNP
- rs150700470
- Type
- single nucleotide variant
- Location
- chr14:95210819 (GRCh38)
- Gene constraint
- LOEUF 0.755 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.84
- Residue 223
- the calponin-homology (ch) 2 domain; the 'actin-binding' region
Similar variants
- CLMN p.Ala223Gly Uncertain significance ★ ⚠ same residue
- CLMN c.2511+10C>T Benign ★★ same type
- CLMN c.886-4G>T Likely benign ★★ same type
- CLMN p.Asp592= Benign ★★ same type
- CLMN p.Glu276Lys Likely benign ★★ same type
- CLMN p.Glu357Lys Benign ★★ same type
- CLMN p.Glu771Ala Likely benign ★★ same type
- CLMN p.His518= 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/clmn-p-ala223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown