CLVS2 p.Ala193=
c.579G>A · rs369441088 · VCV2656896
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.743%, 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 -0.2 | GERP -3.8 |
| Overall | ||
| CADD | 5.628 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.743%
Middle Eastern · 45/6,056 alleles
Filtering AF
0.571%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.51%
Overall
0.00931%
150/1,611,182 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.743% | 135 |
| Admixed American | 0.02% | 4,991 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,670 |
| South Asian | 0.00991% | 10,092 |
| European (non-Finnish) | 0.00603% | 16,592 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,522 |
| African / African-American | 0.00134% | 74,846 |
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
- CLVS2
- Protein
- p.Ala193=
- Coding
- c.579G>A
- MANE Select
- NM_001010852
- dbSNP
- rs369441088
- Type
- single nucleotide variant
- Location
- chr6:123048636 (GRCh38)
- Gene constraint
- LOEUF 0.968 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.15
- Residue 193
- the cral-trio domain
Similar variants
- CLVS2 p.Ala139Gly Uncertain significance ★ ⚠ same type
- CLVS2 p.Ala146Thr Uncertain significance ★ ⚠ same type
- CLVS2 p.Arg138Gly Uncertain significance ★ ⚠ same type
- CLVS2 p.Arg215Trp Uncertain significance ★ ⚠ same type
- CLVS2 p.Arg48Cys Uncertain significance ★ ⚠ same type
- CLVS2 p.Asp272Gly Uncertain significance ★ ⚠ same type
- CLVS2 p.Glu19Gln Uncertain significance ★ same type
- CLVS2 p.Glu316Gly 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/clvs2-p-ala193 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown