Is DRC2 p.Lys320del (c.957GAA[1]) pathogenic?

DRC2 p.Lys320del (c.957GAA[1]) is classified Uncertain significance in DRC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-14). Very rare (popmax 0.00661%, nfe); Associated with primary ciliary dyskinesia 27.

What condition is associated with DRC2 p.Lys320del (c.957GAA[1])?

DRC2 p.Lys320del (c.957GAA[1]) is associated with primary ciliary dyskinesia 27 (ClinVar).

How common is DRC2 p.Lys320del (c.957GAA[1]) in the general population?

DRC2 p.Lys320del (c.957GAA[1]) is very rare (popmax 0.00661%, 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.Lys320del

c.957GAA[1] · rs757225412 · VCV1926102

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00661%, nfe)

Conditions

primary ciliary dyskinesia 27

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 3.3	GERP 1.4, phastCons 1
Overall
CADD	13.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00661% European (non-Finnish) · 78/1,180,032 alleles

Filtering AF 0.00538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00498%

Overall 0.0057% 92/1,614,020 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0096%	10,415
European (non-Finnish)grpmax	0.00661%	15,129
South Asian	0.00659%	15,181
Finnishnot grpmax-eligible	0.00156%	64,036
African / African-American	0.00134%	74,900

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys320del
Coding: c.957GAA[1]
MANE Select: NM_033124
dbSNP: rs757225412
Type: Microsatellite
Location: chr12:48918833 (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.Ile293fs Pathogenic/Likely pathogenic ★★ same condition
DRC2 p.Thr237fs Pathogenic ★ same condition
CCDC65 p.Glu51del Uncertain significance ★ same condition
DRC2 p.Glu220del Uncertain significance ★ same condition
DRC2 p.Lys320Arg Uncertain significance ★ ⚠ same residue
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-lys320del (accessed [today's date]).

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