Is DRC2 p.Thr237fs (c.710_711del) pathogenic?

DRC2 p.Thr237fs (c.710711del) is classified Pathogenic in DRC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-22). Very rare (popmax 0.00271%, nfe); Associated with primary ciliary dyskinesia 27.

What condition is associated with DRC2 p.Thr237fs (c.710_711del)?

DRC2 p.Thr237fs (c.710_711del) is associated with primary ciliary dyskinesia 27 (ClinVar).

How common is DRC2 p.Thr237fs (c.710_711del) in the general population?

DRC2 p.Thr237fs (c.710_711del) is very rare (popmax 0.00271%, 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.Thr237fs

c.710_711del · VCV3667024

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00271%, 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 5 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 1.5, phastCons 1
Overall
CADD	33.0	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 0.00271% European (non-Finnish) · 32/1,180,020 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00204% 33/1,613,996 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,876
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Thr237fs
Coding: c.710_711del
MANE Select: NM_033124
Type: Microsatellite
Location: chr12:48918373 (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 p.Thr237Ile Uncertain significance ★ ⚠ same residue
DRC2 p.Ile293fs Pathogenic/Likely pathogenic ★★ same condition
CCDC65 p.Glu51del Uncertain significance ★ same condition
DRC2 p.Glu220del Uncertain significance ★ same condition
DRC2 p.Lys320del Uncertain significance ★ same condition
DRC2 p.Ser446fs Uncertain significance ★ same condition
DRC2 p.Glu165fs Pathogenic ★★ same condition
CCDC65 p.Arg70Gln 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/drc2-p-thr237fs (accessed [today's date]).

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