Is DRC4 p.Asn243= (c.729C>T) pathogenic?

DRC4 p.Asn243= (c.729C>T) is classified Likely benign in DRC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). Very rare (popmax 0.00113%, sas); Associated with primary ciliary dyskinesia 33.

What condition is associated with DRC4 p.Asn243= (c.729C>T)?

DRC4 p.Asn243= (c.729C>T) is associated with primary ciliary dyskinesia 33 (ClinVar).

How common is DRC4 p.Asn243= (c.729C>T) in the general population?

DRC4 p.Asn243= (c.729C>T) is very rare (popmax 0.00113%, sas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DRC4 p.Asn243=

c.729C>T · rs778991244 · VCV2980436

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00113%, sas)

Conditions

primary ciliary dyskinesia 33

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	phastCons 1
Overall
CADD	9.492	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00113% South Asian · 1/88,372 alleles

Filtering AF 0.000505% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000369%

Overall 0.000817% 13/1,591,188 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0016%	62,696
South Asiangrpmax	0.00113%	88,372
European (non-Finnish)	0.000942%	106,178

Finnish 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: DRC4
Protein: p.Asn243=
Coding: c.729C>T
MANE Select: NM_001481
dbSNP: rs778991244
Type: single nucleotide variant
Location: chr16:90036559 (GRCh38)
Structure: AlphaFold pLDDT 85.12 · 1 PDB
Residue 243: the 'microtubule-binding' region; a UniProt-annotated variant site (in cild33; loss of localization to cilia; abnormal cilia with axonemal disorganization)

Full DRC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 33 — 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

DRC4 p.Asn243His Uncertain significance ★ same residue
DRC4 c.495+1G>T Likely pathogenic ★★ same condition
DRC4 p.Gln357Ter Pathogenic ★★ same condition
DRC4 p.Ala280Thr Uncertain significance ★★ ⚠ same condition
DRC4 p.Ala460Pro Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg143Trp Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg164Trp Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg203Gln 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/drc4-p-asn243 (accessed [today's date]).

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