Is DRC2 p.Glu140= (c.420A>G) pathogenic?

DRC2 p.Glu140= (c.420A>G) is classified Likely benign in DRC2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-07-28). Absent from gnomAD v4.1; Associated with CCDC65-related disorder.

What condition is associated with DRC2 p.Glu140= (c.420A>G)?

DRC2 p.Glu140= (c.420A>G) is associated with CCDC65-related disorder (ClinVar).

How common is DRC2 p.Glu140= (c.420A>G) in the general population?

DRC2 p.Glu140= (c.420A>G) is absent from gnomAD v4.1 (gnomAD).

DRC2 p.Glu140=

c.420A>G · rs2498836038 · VCV3046255

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

CCDC65-related disorder

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 0.22	GERP -0.54, phastCons 0.2
Overall
CADD	6.513	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DRC2
Protein: p.Glu140=
Coding: c.420A>G
MANE Select: NM_033124
dbSNP: rs2498836038
Type: single nucleotide variant
Location: chr12:48914523 (GRCh38)
Structure: AlphaFold pLDDT 83.21 · 1 PDB

Full DRC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CCDC65-related disorder

Similar variants

CCDC65 p.Arg70Gln Uncertain significance ★★ ⚠ same type
CCDC65 p.Glu110Lys Uncertain significance ★★ ⚠ same type
CCDC65 p.Lys158Asn Uncertain significance ★★ ⚠ same type
DRC2 p.Ala109Val Uncertain significance ★★ ⚠ same type
DRC2 p.Ala114Pro Uncertain significance ★★ ⚠ same type
DRC2 p.Arg118Cys Uncertain significance ★★ ⚠ same type
DRC2 p.Arg294His Uncertain significance ★★ ⚠ same type
DRC2 p.Arg315Gln Uncertain significance ★★ ⚠ same type

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-glu140 (accessed [today's date]).

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