Is DRC1 p.Arg117fs (c.344dup) pathogenic?

DRC1 p.Arg117fs (c.344dup) is classified Pathogenic in DRC1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-01-11). Very rare (popmax 0.00333%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with DRC1 p.Arg117fs (c.344dup)?

DRC1 p.Arg117fs (c.344dup) is associated with primary ciliary dyskinesia (ClinVar).

How common is DRC1 p.Arg117fs (c.344dup) in the general population?

DRC1 p.Arg117fs (c.344dup) is very rare (popmax 0.00333%, 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.Arg117fs

c.344dup · rs747358703 · VCV1457351

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

primary ciliary dyskinesia

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 3 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP -3.2

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,974 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00151% 22/1,460,796 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,987
European (non-Finnish)	0.00161%	62,069
Remaining individualsnot grpmax-eligible	0.0016%	62,428

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.Arg117fs
Coding: c.344dup
MANE Select: NM_145038
dbSNP: rs747358703
Type: Duplication
Location: chr2:26421387 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.44 · 1 PDB
Residue 117: a UniProt-annotated variant site (in spgf80)

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.Arg117His Uncertain significance ★★ ⚠ same residue
DRC1 p.Gln37fs Pathogenic/Likely pathogenic ★★ same condition
DRC1 p.Val690fs Pathogenic ★★ same condition
DRC1 p.Thr732fs Uncertain significance ★★ same condition
DRC1 c.889-9dup Benign/Likely benign ★★ same condition
DRC1 p.Ile225fs Pathogenic ★ same condition
DRC1 p.Arg117Cys Uncertain significance ★ ⚠ same residue
DRC1 p.Ile36_Arg40dup Uncertain significance ★ 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-arg117fs (accessed [today's date]).

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