Is DRC2 p.Leu384= (c.1152A>T) pathogenic?

DRC2 p.Leu384= (c.1152A>T) is classified Likely benign in DRC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-25). Ultra-rare (popmax 0.0201%, eas).

How common is DRC2 p.Leu384= (c.1152A>T) in the general population?

DRC2 p.Leu384= (c.1152A>T) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

DRC2 p.Leu384=

c.1152A>T · rs1178967329 · VCV752064

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

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 -2.4	GERP -3.1
Overall
CADD	0.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% East Asian · 9/44,856 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0078%

Overall 0.000616% 9/1,460,272 alleles · ultra-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.Leu384=
Coding: c.1152A>T
MANE Select: NM_033124
dbSNP: rs1178967329
Type: single nucleotide variant
Location: chr12:48921055 (GRCh38)
Structure: AlphaFold pLDDT 83.21 · 1 PDB

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

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-leu384 (accessed [today's date]).

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