Is DRC2 p.Asp125= (c.375C>T) pathogenic?

DRC2 p.Asp125= (c.375C>T) is classified Benign/Likely benign in DRC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-21). Rare (popmax 0.357%, afr); Associated with primary ciliary dyskinesia 27.

What condition is associated with DRC2 p.Asp125= (c.375C>T)?

DRC2 p.Asp125= (c.375C>T) is associated with primary ciliary dyskinesia 27 (ClinVar).

How common is DRC2 p.Asp125= (c.375C>T) in the general population?

DRC2 p.Asp125= (c.375C>T) is rare (popmax 0.357%, afr) (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.Asp125=

c.375C>T · rs143088014 · VCV474639

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.357%, afr)

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 0.23	GERP -0.61, phastCons 0.98
Overall
CADD	8.134	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.357% African / African-American · 268/75,052 alleles

Filtering AF 0.322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.308%

Overall 0.0185% 298/1,614,206 alleles · rare exomes 145/1,461,876 · genomes 153/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.357%	280
Remaining individualsnot grpmax-eligible	0.0256%	3,907
Admixed American	0.015%	6,669
European (non-Finnish)	0.000424%	236,005

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.Asp125=
Coding: c.375C>T
MANE Select: NM_033124
dbSNP: rs143088014
Type: single nucleotide variant
Location: chr12:48914478 (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-asp125 (accessed [today's date]).

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