DCLRE1C p.Cys61Arg
c.181T>C · rs1589136760 · VCV648095
ClinGen expert panel — Severe Combined Immunodeficiency Disease VCEP
Uncertain Significance for severe combined immunodeficiency due to DCLRE1C deficiency. Applied ACMG criteria (verbatim):
PM2_Supporting
Curation rationale (ClinGen, verbatim)
The c.181T>C (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause substitution of Cysteine by Arginine at amino acid 61 (p.Cys61Arg). This variant is absent from gnomAD v4 (PM2_Supporting). To our knowledge, this variant has not been reported in the literature in individuals affected with DCLRE1C-related conditions or in functional studies. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive severe combined immunodeficiency due to DCLRE1C deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP. Criteria applied: PM2_Supporting (VCEP specifications version 1.0).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| AlphaMissense | 0.998 | likely pathogenic · top 2% in DCLRE1C |
|---|---|---|
| REVEL | 0.906 | moderately pathogenic-leaning |
| SaProt | LLR -16.13 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | phastCons 1 |
| Regional constraint | o/e 1.08 | unconstrained · MANE · 46 kb · p 0.034 · regional, not allelic |
| Overall | ||
| CADD | 29.1 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- DCLRE1C
- Protein
- p.Cys61Arg
- Coding
- c.181T>C
- MANE Select
- NM_001033855
- dbSNP
- rs1589136760
- Type
- single nucleotide variant
- Location
- chr10:14945170 (GRCh38)
- Gene constraint
- LOEUF 0.866 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 70.10 · 14 PDB
- Residue 61
- a β-strand
Disease context
severe combined immunodeficiency due to DCLRE1C deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Severe combined immunodeficiency due to DCLRE1C deficiency (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- DCLRE1C p.Cys61= Likely benign ★ same residue
- DCLRE1C p.Cys61fs Pathogenic ★ same residue
- DCLRE1C c.109+1G>T Pathogenic ★★★ same condition
- DCLRE1C c.161+2T>G Pathogenic ★★★ same condition
- DCLRE1C p.Ala28Pro Likely pathogenic ★★★ same condition
- DCLRE1C p.Arg191Ter Pathogenic ★★★ same condition
- DCLRE1C p.Arg383Ter Pathogenic ★★★ same condition
- DCLRE1C p.Arg81Ter Pathogenic ★★★ 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/dclre1c-p-cys61arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown