Is DRC4 p.Leu367= (c.1101A>G) pathogenic?

DRC4 p.Leu367= (c.1101A>G) is classified Likely benign in DRC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-09). Ultra-rare (popmax 0.0199%, sas); Associated with primary ciliary dyskinesia 33.

What condition is associated with DRC4 p.Leu367= (c.1101A>G)?

DRC4 p.Leu367= (c.1101A>G) is associated with primary ciliary dyskinesia 33 (ClinVar).

How common is DRC4 p.Leu367= (c.1101A>G) in the general population?

DRC4 p.Leu367= (c.1101A>G) is ultra-rare (popmax 0.0199%, 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.Leu367=

c.1101A>G · rs772281893 · VCV2754495

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0199%, 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 0.73	phastCons 1
Overall
CADD	15.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0199% South Asian · 18/90,532 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00211% 34/1,611,672 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0199%	5,030
Remaining individualsnot grpmax-eligible	0.00641%	15,592
European (non-Finnish)	0.00102%	98,253

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.Leu367=
Coding: c.1101A>G
MANE Select: NM_001481
dbSNP: rs772281893
Type: single nucleotide variant
Location: chr16:90040389 (GRCh38)
Structure: AlphaFold pLDDT 85.12 · 1 PDB
Residue 367: a UniProt-annotated variant site (in cild33; loss of localization to cilia; abnormal cilia with axonemal disorganization); the 'interaction with smo' region

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 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
DRC4 p.Arg278Cys 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-leu367 (accessed [today's date]).

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