Is DRP2 p.Thr378= (c.1134A>G) pathogenic?

DRP2 p.Thr378= (c.1134A>G) is classified Uncertain significance in DRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). Very rare (popmax 0.00173%, afr).

How common is DRP2 p.Thr378= (c.1134A>G) in the general population?

DRP2 p.Thr378= (c.1134A>G) is very rare (popmax 0.00173%, afr) (gnomAD).

DRP2 p.Thr378=

c.1134A>G · rs763727945 · VCV2033539

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00173%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.26	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.42	GERP -3.7, phastCons 0.79
Overall
CADD	13.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00173% African / African-American · 1/57,790 alleles

Overall 9.15e-05% 1/1,092,554 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: DRP2
Protein: p.Thr378=
Coding: c.1134A>G
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs763727945
Type: single nucleotide variant
Location: chrX:101245406 (GRCh38)
Structure: AlphaFold pLDDT 90.49 · 15 PDB
Residue 378: an α-helix

Full DRP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRP2 p.Thr378Ala Uncertain significance ★ ⚠ same residue
DRP2 p.Glu432Ter Pathogenic ★★ same type
DPYSL2 p.Asn492Ser Uncertain significance ★★ ⚠ same type
DPYSL2 p.Asp520Asn Uncertain significance ★★ ⚠ same type
DRP2 p.Ala205Val Uncertain significance ★★ ⚠ same type
DRP2 p.Ala643Thr Uncertain significance ★★ ⚠ same type
DRP2 p.Arg199His Uncertain significance ★★ ⚠ same type
DRP2 p.Arg224Cys 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/drp2-p-thr378 (accessed [today's date]).

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