Is DRC2 p.Asp199= (c.597T>C) pathogenic?

DRC2 p.Asp199= (c.597T>C) is classified Likely benign in DRC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-30). Ultra-rare (popmax 0.049%, eas); Associated with primary ciliary dyskinesia 27.

What condition is associated with DRC2 p.Asp199= (c.597T>C)?

DRC2 p.Asp199= (c.597T>C) is associated with primary ciliary dyskinesia 27 (ClinVar).

How common is DRC2 p.Asp199= (c.597T>C) in the general population?

DRC2 p.Asp199= (c.597T>C) is ultra-rare (popmax 0.049%, eas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DRC2 p.Asp199=

c.597T>C · rs367593202 · VCV698837

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.049%, eas)

Conditions

primary ciliary dyskinesia 27

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 0.17	GERP -2.8, phastCons 0.99
Overall
CADD	7.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.049% East Asian · 22/44,866 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.00285% 46/1,613,950 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.049%	2,039
Remaining individualsnot grpmax-eligible	0.0176%	5,682
South Asian	0.011%	9,105
European (non-Finnish)	0.000254%	393,315

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.Asp199=
Coding: c.597T>C
MANE Select: NM_033124
dbSNP: rs367593202
Type: single nucleotide variant
Location: chr12:48917096 (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 condition
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-asp199 (accessed [today's date]).

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