Is DRC4 p.Arg342Pro (c.1025G>C) pathogenic?

DRC4 p.Arg342Pro (c.1025G>C) is classified Uncertain significance in DRC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-17). AlphaMissense: likely pathogenic (0.9648); Very rare (popmax 0.00178%, amr); Associated with primary ciliary dyskinesia 33.

What condition is associated with DRC4 p.Arg342Pro (c.1025G>C)?

DRC4 p.Arg342Pro (c.1025G>C) is associated with primary ciliary dyskinesia 33 (ClinVar).

How common is DRC4 p.Arg342Pro (c.1025G>C) in the general population?

DRC4 p.Arg342Pro (c.1025G>C) is very rare (popmax 0.00178%, amr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

What do computational predictors say about DRC4 p.Arg342Pro (c.1025G>C)?

AlphaMissense predicts likely pathogenic (score 0.9648) — an in-silico prediction, not a clinical call.

DRC4 p.Arg342Pro

c.1025G>C · rs532241934 · VCV1007085

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9648 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 33

Computational evidence

Protein change
AlphaMissense	0.9648	likely pathogenic · top 1% in DRC4
REVEL	0.682	pathogenic-leaning
SaProt	LLR -12.57	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 21 kb · p 0.0024 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% Admixed American · 1/56,316 alleles

Overall 0.00197% 3/152,212 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00178%	56,316
Remaining individualsnot grpmax-eligible	0.00163%	61,480
African / African-American	0.00135%	74,310

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.Arg342Pro
Coding: c.1025G>C
MANE Select: NM_001481
dbSNP: rs532241934
Type: single nucleotide variant
Location: chr16:90040313 (GRCh38)
Structure: AlphaFold pLDDT 85.12 · 1 PDB
Residue 342: 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.Arg342Trp Uncertain significance ★★ ⚠ same residue
DRC4 p.Arg342= Likely benign ★ same residue
DRC4 p.Arg342Gln 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

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-arg342pro (accessed [today's date]).

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