Is DRC2 p.Arg70Trp (c.208C>T) pathogenic?

DRC2 p.Arg70Trp (c.208C>T) is classified Uncertain significance in DRC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). AlphaMissense: likely benign (0.2992); Ultra-rare (popmax 0.0725%, sas); Associated with primary ciliary dyskinesia 27.

What condition is associated with DRC2 p.Arg70Trp (c.208C>T)?

DRC2 p.Arg70Trp (c.208C>T) is associated with primary ciliary dyskinesia 27 (ClinVar).

How common is DRC2 p.Arg70Trp (c.208C>T) in the general population?

DRC2 p.Arg70Trp (c.208C>T) is ultra-rare (popmax 0.0725%, sas) (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 DRC2 p.Arg70Trp (c.208C>T)?

AlphaMissense predicts likely benign (score 0.2992) — an in-silico prediction, not a clinical call.

DRC2 p.Arg70Trp

c.208C>T · rs748450007 · VCV2044463

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2992 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0725%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

primary ciliary dyskinesia 27

Computational evidence

Protein change
AlphaMissense	0.2992	likely benign
REVEL	0.542	indeterminate
SaProt	LLR -11.82	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -1.1, phastCons 0.76
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.19 · regional, not allelic
Overall
CADD	25.0	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

Grpmax group 0.0725% South Asian · 66/91,044 alleles

Filtering AF 0.0584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0533%

Overall 0.00459% 74/1,613,852 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0725%	1,379
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Remaining individualsnot grpmax-eligible	0.0032%	31,241
East Asian	0.00223%	44,896
European (non-Finnish)	0.000339%	294,977

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: DRC2
Protein: p.Arg70Trp
Coding: c.208C>T
MANE Select: NM_033124
dbSNP: rs748450007
Type: single nucleotide variant
Location: chr12:48905021 (GRCh38)
Structure: AlphaFold pLDDT 83.21 · 1 PDB

Full DRC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 27 — 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

CCDC65 p.Arg70Gln Uncertain significance ★★ ⚠ same residue
CCDC65 p.Glu110Lys Uncertain significance ★★ ⚠ same condition
CCDC65 p.Lys158Asn Uncertain significance ★★ ⚠ same condition
DRC2 p.Ala109Val Uncertain significance ★★ ⚠ same condition
DRC2 p.Ala114Pro Uncertain significance ★★ ⚠ same condition
DRC2 p.Arg118Cys Uncertain significance ★★ ⚠ same condition
DRC2 p.Arg294His Uncertain significance ★★ ⚠ same condition
DRC2 p.Arg315Gln 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/drc2-p-arg70trp (accessed [today's date]).

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