Is DRC4 p.Ser27Arg (c.81C>G) pathogenic?

DRC4 p.Ser27Arg (c.81C>G) is classified Uncertain significance in DRC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-21). AlphaMissense: ambiguous (0.5295); Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia 33.

What condition is associated with DRC4 p.Ser27Arg (c.81C>G)?

DRC4 p.Ser27Arg (c.81C>G) is associated with primary ciliary dyskinesia 33 (ClinVar).

How common is DRC4 p.Ser27Arg (c.81C>G) in the general population?

DRC4 p.Ser27Arg (c.81C>G) 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.Ser27Arg (c.81C>G)?

AlphaMissense predicts ambiguous (score 0.5295) — an in-silico prediction, not a clinical call.

DRC4 p.Ser27Arg

c.81C>G · rs2151276720 · VCV1050909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5295 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

primary ciliary dyskinesia 33

Computational evidence

Protein change
AlphaMissense	0.5295	ambiguous
REVEL	0.086	moderately benign-leaning
SaProt	LLR -10.14	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.92, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 21 kb · p 0.0024 · regional, not allelic
Overall
CADD	23.3	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.Ser27Arg
Coding: c.81C>G
MANE Select: NM_001481
dbSNP: rs2151276720
Type: single nucleotide variant
Location: chr16:90027713 (GRCh38)
Structure: AlphaFold pLDDT 85.12 · 1 PDB
Residue 27: the 'regulates microtubule-binding' region; the 'disordered' 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-ser27arg (accessed [today's date]).

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