Is DRC1 p.Gln37fs (c.109dup) pathogenic?

DRC1 p.Gln37fs (c.109dup) is classified Pathogenic/Likely pathogenic in DRC1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-03-01). Ultra-rare (popmax 0.0495%, mid); Associated with primary ciliary dyskinesia 21.

What condition is associated with DRC1 p.Gln37fs (c.109dup)?

DRC1 p.Gln37fs (c.109dup) is associated with primary ciliary dyskinesia 21, primary ciliary dyskinesia (ClinVar).

How common is DRC1 p.Gln37fs (c.109dup) in the general population?

DRC1 p.Gln37fs (c.109dup) is ultra-rare (popmax 0.0495%, mid) (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.Gln37fs

c.109dup · rs750136163 · VCV663966

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Conditions

primary ciliary dyskinesia 21

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 1 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00335% 54/1,612,494 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
Admixed American	0.0317%	3,157
Remaining individualsnot grpmax-eligible	0.00801%	12,486
European (non-Finnish)	0.00229%	43,688

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.Gln37fs
Coding: c.109dup
MANE Select: NM_145038
dbSNP: rs750136163
Type: Duplication
Location: chr2:26402096 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.44 · 1 PDB

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

Disease context

primary ciliary dyskinesia 21 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

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.Val690fs Pathogenic ★★ same condition
DRC1 p.Thr732fs Uncertain significance ★★ same condition
DRC1 c.889-9dup Benign/Likely benign ★★ same condition
DRC1 p.Arg117fs Pathogenic ★ same condition
DRC1 p.Ile225fs Pathogenic ★ same condition
DRC1 p.Ile36_Arg40dup Uncertain significance ★ same condition
DRC1 c.1600-3dup Benign ★ same condition
DRC1 c.244-14dup Likely 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/drc1-p-gln37fs (accessed [today's date]).

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