Is DRC2 p.Glu165fs (c.494del) pathogenic?

DRC2 p.Glu165fs (c.494del) is classified Pathogenic in DRC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-11-19). Very rare (popmax 0.000254%, nfe); Associated with primary ciliary dyskinesia 27.

What condition is associated with DRC2 p.Glu165fs (c.494del)?

DRC2 p.Glu165fs (c.494del) is associated with primary ciliary dyskinesia 27 (ClinVar).

How common is DRC2 p.Glu165fs (c.494del) in the general population?

DRC2 p.Glu165fs (c.494del) is very rare (popmax 0.000254%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DRC2 p.Glu165fs

c.494del · rs1555174708 · VCV474640

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

primary ciliary dyskinesia 27

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,932 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,748 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: DRC2
Protein: p.Glu165fs
Coding: c.494del
MANE Select: NM_033124
dbSNP: rs1555174708
Type: Deletion
Location: chr12:48916993 (GRCh38)
Structure: AlphaFold pLDDT 83.21 · 1 PDB

Full DRC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 27 — 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

DRC2 c.1026+8_1026+9del Benign/Likely benign ★★ same condition
DRC2 p.Asn232_Tyr233insTer Pathogenic ★ same condition
DRC2 p.Leu247fs Pathogenic ★ same condition
DRC2 p.Val302fs Pathogenic ★ same condition
DRC2 p.Val323fs Pathogenic ★ same condition
CCDC65 p.Phe457fs Uncertain significance ★ same condition
DRC2 p.Lys49_Ala55del Uncertain significance ★ same condition
DRC2 c.1179+14del Benign ★ 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/drc2-p-glu165fs (accessed [today's date]).

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