Is DRC4 p.Arg44= (c.132C>T) pathogenic?

DRC4 p.Arg44= (c.132C>T) is classified Benign in DRC4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 65.3%, eas) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia 33.

What condition is associated with DRC4 p.Arg44= (c.132C>T)?

DRC4 p.Arg44= (c.132C>T) is associated with primary ciliary dyskinesia 33 (ClinVar).

How is Primary ciliary dyskinesia inherited?

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

DRC4 p.Arg44=

Q: How common is DRC4 p.Arg44= (c.132C>T) in the general population?

DRC4 p.Arg44= (c.132C>T) is common (popmax 65.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.132C>T · rs2302513 · VCV1170264

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 65.3%, eas) — too common for a highly-penetrant pathogenic allele

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 -20
Overall
CADD	0.113	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 65.3% East Asian · 29,269/44,848 alleles

Filtering AF 64.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 64.4%

Overall 12.8% 206,956/1,613,226 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	65.3%	2
Admixed American	31.3%	3
Finnishnot grpmax-eligible	28.3%	4
South Asian	13.9%	7
Remaining individualsnot grpmax-eligible	13.2%	8
African / African-American	12.4%	8
European (non-Finnish)	9.2%	11
Middle Eastern	6.9%	14
Ashkenazi Jewishnot grpmax-eligible	5.98%	17
Amishnot grpmax-eligible	2.63%	38

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.Arg44=
Coding: c.132C>T
MANE Select: NM_001481
dbSNP: rs2302513
Type: single nucleotide variant
Location: chr16:90031340 (GRCh38)
Structure: AlphaFold pLDDT 85.12 · 1 PDB
Residue 44: the 'regulates microtubule-binding' 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 p.Arg44His 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-arg44 (accessed [today's date]).

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