Is DRC2 p.Gln112Lys (c.334C>A) pathogenic?

DRC2 p.Gln112Lys (c.334C>A) is classified Uncertain significance in DRC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-12). AlphaMissense: ambiguous (0.4284); Ultra-rare (popmax 0.0784%, amr); Associated with primary ciliary dyskinesia 27.

What condition is associated with DRC2 p.Gln112Lys (c.334C>A)?

DRC2 p.Gln112Lys (c.334C>A) is associated with primary ciliary dyskinesia 27 (ClinVar).

How common is DRC2 p.Gln112Lys (c.334C>A) in the general population?

DRC2 p.Gln112Lys (c.334C>A) is ultra-rare (popmax 0.0784%, amr) (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.Gln112Lys (c.334C>A)?

AlphaMissense predicts ambiguous (score 0.4284) — an in-silico prediction, not a clinical call.

DRC2 p.Gln112Lys

c.334C>A · rs750352672 · VCV1480959

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4284 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0784%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

primary ciliary dyskinesia 27

Computational evidence

Protein change
AlphaMissense	0.4284	ambiguous
REVEL	0.275	benign-leaning
SaProt	LLR -6.31	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.19 · regional, not allelic
Overall
CADD	23.8	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 0.0784% Admixed American · 47/59,968 alleles

Filtering AF 0.0605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.00297% 48/1,613,604 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0784%	1,276
Remaining individualsnot grpmax-eligible	0.0016%	62,454

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.Gln112Lys
Coding: c.334C>A
MANE Select: NM_033124
dbSNP: rs750352672
Type: single nucleotide variant
Location: chr12:48914437 (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-gln112lys (accessed [today's date]).

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