Is DCLRE1C p.Asp552= (c.1656C>T) pathogenic?

DCLRE1C p.Asp552= (c.1656C>T) is classified Likely benign in DCLRE1C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-14). Very rare (popmax 0.00534%, afr); Associated with severe combined immunodeficiency due to DCLRE1C deficiency.

What condition is associated with DCLRE1C p.Asp552= (c.1656C>T)?

DCLRE1C p.Asp552= (c.1656C>T) is associated with severe combined immunodeficiency due to DCLRE1C deficiency (ClinVar).

How common is DCLRE1C p.Asp552= (c.1656C>T) in the general population?

DCLRE1C p.Asp552= (c.1656C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

DCLRE1C p.Asp552=

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.1656C>T · VCV4810910

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

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 1.1	phastCons 1
Overall
CADD	5.648	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,934 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000372% 6/1,614,104 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,734
South Asian	0.0022%	45,541

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.Asp552=
Coding: c.1656C>T
MANE Select: NM_001033855
Type: single nucleotide variant
Location: chr10:14908831 (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 552: the 'disordered' region

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 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
DCLRE1C p.Cys116Arg 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-asp552 (accessed [today's date]).

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