Is DCLRE1C p.Cys61= (c.183T>C) pathogenic?

DCLRE1C p.Cys61= (c.183T>C) is classified Likely benign in DCLRE1C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-22). Very rare (popmax 0.00333%, amr); Associated with severe combined immunodeficiency due to DCLRE1C deficiency.

What condition is associated with DCLRE1C p.Cys61= (c.183T>C)?

DCLRE1C p.Cys61= (c.183T>C) is associated with severe combined immunodeficiency due to DCLRE1C deficiency (ClinVar).

How common is DCLRE1C p.Cys61= (c.183T>C) in the general population?

DCLRE1C p.Cys61= (c.183T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

DCLRE1C p.Cys61=

Q: How is Severe combined immunodeficiency due to DCLRE1C deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.183T>C · rs2131108523 · VCV1141300

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

severe combined immunodeficiency due to DCLRE1C deficiency

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 2.5	phastCons 1
Overall
CADD	8.686	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,994 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,460,890 alleles · very rare

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: DCLRE1C
Protein: p.Cys61=
Coding: c.183T>C
MANE Select: NM_001033855
dbSNP: rs2131108523
Type: single nucleotide variant
Location: chr10:14945168 (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

Full DCLRE1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

severe combined immunodeficiency due to DCLRE1C deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe combined immunodeficiency due to DCLRE1C deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DCLRE1C p.Cys61Arg Uncertain significance ★★★ ⚠ 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-cys61 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown