Is DRC2 p.Met1Lys (c.2T>A) pathogenic?

DRC2 p.Met1Lys (c.2T>A) is classified Uncertain significance in DRC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-28). Very rare (popmax 0.00134%, afr); Associated with primary ciliary dyskinesia 27.

What condition is associated with DRC2 p.Met1Lys (c.2T>A)?

DRC2 p.Met1Lys (c.2T>A) is associated with primary ciliary dyskinesia 27 (ClinVar).

How common is DRC2 p.Met1Lys (c.2T>A) in the general population?

DRC2 p.Met1Lys (c.2T>A) 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.

DRC2 p.Met1Lys

c.2T>A · rs1939435183 · VCV1010054

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

primary ciliary dyskinesia 27

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.268	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,904 alleles

Overall 6.85e-05% 1/1,460,846 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: DRC2
Protein: p.Met1Lys
Coding: c.2T>A
MANE Select: NM_033124
dbSNP: rs1939435183
Type: single nucleotide variant
Location: chr12:48904338 (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-met1lys (accessed [today's date]).

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