Is DRP2 p.Leu595Val (c.1783C>G) pathogenic?

DRP2 p.Leu595Val (c.1783C>G) is classified Uncertain significance in DRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). AlphaMissense: likely pathogenic (0.6189); Absent from gnomAD v4.1.

How common is DRP2 p.Leu595Val (c.1783C>G) in the general population?

DRP2 p.Leu595Val (c.1783C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DRP2 p.Leu595Val (c.1783C>G)?

AlphaMissense predicts likely pathogenic (score 0.6189) — an in-silico prediction, not a clinical call.

DRP2 p.Leu595Val

c.1783C>G · VCV3644844

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6189 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6189	likely pathogenic
REVEL	0.669	pathogenic-leaning
SaProt	LLR -10.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.098	GERP 0.96, phastCons 0.9
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: DRP2
Protein: p.Leu595Val
Coding: c.1783C>G
MANE Select: NM_001197293 · reported on NM_001939
Type: single nucleotide variant
Location: chrX:101251001 (GRCh38)
Structure: AlphaFold pLDDT 90.49 · 15 PDB

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

Similar variants

DPYSL2 p.Glu595Asp 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-leu595val (accessed [today's date]).

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