Is DRC1 p.Arg39Pro (c.116G>C) pathogenic?

DRC1 p.Arg39Pro (c.116G>C) is classified Uncertain significance in DRC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-25). AlphaMissense: likely pathogenic (0.9875); Very rare (popmax 0.00134%, afr); Associated with primary ciliary dyskinesia 21.

What condition is associated with DRC1 p.Arg39Pro (c.116G>C)?

DRC1 p.Arg39Pro (c.116G>C) is associated with primary ciliary dyskinesia 21 (ClinVar).

How common is DRC1 p.Arg39Pro (c.116G>C) in the general population?

DRC1 p.Arg39Pro (c.116G>C) is very rare (popmax 0.00134%, afr) (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 DRC1 p.Arg39Pro (c.116G>C)?

AlphaMissense predicts likely pathogenic (score 0.9875) — an in-silico prediction, not a clinical call.

DRC1 p.Arg39Pro

c.116G>C · rs1261893984 · VCV2428723

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9875 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

primary ciliary dyskinesia 21

Computational evidence

Protein change
AlphaMissense	0.9875	likely pathogenic · top 1% in DRC1
REVEL	0.322	indeterminate
SaProt	LLR -16.16	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 55 kb · p 0.71 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,874 alleles

Overall 0.000657% 1/152,230 alleles · very rare

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: DRC1
Protein: p.Arg39Pro
Coding: c.116G>C
MANE Select: NM_145038
dbSNP: rs1261893984
Type: single nucleotide variant
Location: chr2:26402105 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.44 · 1 PDB

Full DRC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 21 — 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

DRC1 p.Arg39Gly Uncertain significance ★ ⚠ same residue
DRC1 p.Gln118Ter Pathogenic/Likely pathogenic ★★ same condition
DRC1 p.Gln337Ter Pathogenic/Likely pathogenic ★★ same condition
DRC1 p.Ala416Gly Uncertain significance ★★ ⚠ same condition
DRC1 p.Ala473Val Uncertain significance ★★ ⚠ same condition
DRC1 p.Ala475Val Uncertain significance ★★ ⚠ same condition
DRC1 p.His107Asp Uncertain significance ★★ ⚠ same condition
DRC1 p.Lys638Thr 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/drc1-p-arg39pro (accessed [today's date]).

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