Is DCLRE1C p.Arg565= (c.1695A>G) pathogenic?

DCLRE1C p.Arg565= (c.1695A>G) is classified Likely benign in DCLRE1C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-11). Absent from gnomAD v4.1; Associated with severe combined immunodeficiency due to DCLRE1C deficiency.

What condition is associated with DCLRE1C p.Arg565= (c.1695A>G)?

DCLRE1C p.Arg565= (c.1695A>G) is associated with severe combined immunodeficiency due to DCLRE1C deficiency (ClinVar).

How common is DCLRE1C p.Arg565= (c.1695A>G) in the general population?

DCLRE1C p.Arg565= (c.1695A>G) is absent from gnomAD v4.1 (gnomAD).

DCLRE1C p.Arg565=

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.1695A>G · rs2131773917 · VCV1575871

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 3.5	phastCons 1
Overall
CADD	7.368	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

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.Arg565=
Coding: c.1695A>G
MANE Select: NM_001033855
dbSNP: rs2131773917
Type: single nucleotide variant
Location: chr10:14908792 (GRCh38)
Gene constraint: LOEUF 0.866 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 14 PDB

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.Arg565Ile Uncertain significance ★ ⚠ 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
DCLRE1C p.Asp136Asn Likely 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-arg565 (accessed [today's date]).

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