Is DRC4 p.Arg68Ser (c.204G>T) pathogenic?

DRC4 p.Arg68Ser (c.204G>T) is classified Uncertain significance in DRC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: ambiguous (0.4643); Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia 33.

What condition is associated with DRC4 p.Arg68Ser (c.204G>T)?

DRC4 p.Arg68Ser (c.204G>T) is associated with primary ciliary dyskinesia 33 (ClinVar).

How common is DRC4 p.Arg68Ser (c.204G>T) in the general population?

DRC4 p.Arg68Ser (c.204G>T) is absent from gnomAD v4.1 (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.Arg68Ser (c.204G>T)?

AlphaMissense predicts ambiguous (score 0.4643) — an in-silico prediction, not a clinical call.

DRC4 p.Arg68Ser

c.204G>T · VCV4782995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4643 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

primary ciliary dyskinesia 33

Computational evidence

Protein change
AlphaMissense	0.4643	ambiguous
REVEL	0.247	benign-leaning
SaProt	LLR -7.17	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 21 kb · p 0.0024 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DRC4
Protein: p.Arg68Ser
Coding: c.204G>T
MANE Select: NM_001481
Type: single nucleotide variant
Location: chr16:90031412 (GRCh38)
Structure: AlphaFold pLDDT 85.12 · 1 PDB
Residue 68: 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.Arg68= Likely benign ★ 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-arg68ser (accessed [today's date]).

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