Is DRC1 p.Asp501del (c.1503_1505del) pathogenic?

DRC1 p.Asp501del (c.15031505del) is classified Uncertain significance in DRC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-24). Ultra-rare (popmax 0.03%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with DRC1 p.Asp501del (c.1503_1505del)?

DRC1 p.Asp501del (c.1503_1505del) is associated with primary ciliary dyskinesia (ClinVar).

How common is DRC1 p.Asp501del (c.1503_1505del) in the general population?

DRC1 p.Asp501del (c.1503_1505del) is ultra-rare (popmax 0.03%, amr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DRC1 p.Asp501del

c.1503_1505del · rs778078856 · VCV1364773

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.45	GERP -1.6, phastCons 0.22
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.03% Admixed American · 18/60,014 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00112% 18/1,614,066 alleles · ultra-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: DRC1
Protein: p.Asp501del
Coding: c.1503_1505del
MANE Select: NM_145038
dbSNP: rs778078856
Type: Deletion
Location: chr2:26448795 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.44 · 1 PDB
Residue 501: a UniProt-annotated variant site (in cild21; multiple flagellar abnormalities are present in patient sperm); a UniProt-annotated variant site (in spgf80); a UniProt-annotated variant site (in cild21)

Full DRC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DRC1 p.Asp501= Likely benign ★ same residue
DRC1 p.Ser659fs Pathogenic ★★ same condition
DRC1 p.Arg694fs Uncertain significance ★★ same condition
DRC1 p.Lys574_Glu578del Likely benign ★★ same condition
DRC1 p.Asn442fs Pathogenic ★ same condition
DRC1 p.Gln296fs Pathogenic ★ same condition
DRC1 p.Leu518fs Pathogenic ★ same condition
DRC1 p.Lys338fs 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/drc1-p-asp501del (accessed [today's date]).

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