DRC1 p.Cys281=
c.843C>T · rs371207623 · VCV1140862
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
2
Inborn genetic diseases
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 -12 | GERP -3.2 |
| Overall | ||
| CADD | 0.046 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00108%
Overall
0.00192%
31/1,614,116 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
| South Asian | 0.00439% | 22,772 |
| European (non-Finnish) | 0.00195% | 51,304 |
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
- DRC1
- Protein
- p.Cys281=
- Coding
- c.843C>T
- MANE Select
- NM_145038
- dbSNP
- rs371207623
- Type
- single nucleotide variant
- Location
- chr2:26431961 (GRCh38)
- Gene constraint
- LOEUF 0.867 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.44 · 1 PDB
- Residue 281
- a UniProt-annotated variant site (in spgf80); a UniProt-annotated variant site (in cild21)
Similar variants
- DRC1 p.Gln118Ter Pathogenic/Likely pathogenic ★★ same condition
- DRC1 p.Gln337Ter Pathogenic/Likely pathogenic ★★ same condition
- DRC1 p.Ser642Ter Pathogenic/Likely pathogenic ★★ same condition
- DRC1 p.Ala250Val Uncertain significance ★★ ⚠ same condition
- DRC1 p.Ala391Val Uncertain significance ★★ ⚠ same condition
- DRC1 p.Ala416Gly Uncertain significance ★★ ⚠ same condition
- DRC1 p.Ala45Val Uncertain significance ★★ ⚠ same condition
- DRC1 p.Ala473Val Uncertain significance ★★ ⚠ same condition
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/drc1-p-cys281 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown