Is DRP2 p.Arg565His (c.1694G>A) pathogenic?

DRP2 p.Arg565His (c.1694G>A) is classified Uncertain significance in DRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-02). AlphaMissense: likely benign (0.1115); Very rare (popmax 0.00299%, eas).

How common is DRP2 p.Arg565His (c.1694G>A) in the general population?

DRP2 p.Arg565His (c.1694G>A) is very rare (popmax 0.00299%, eas) (gnomAD).

What do computational predictors say about DRP2 p.Arg565His (c.1694G>A)?

AlphaMissense predicts likely benign (score 0.1115) — an in-silico prediction, not a clinical call.

DRP2 p.Arg565His

c.1694G>A · rs778779918 · VCV2993701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1115 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00299%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1115	likely benign
REVEL	0.509	indeterminate
SaProt	LLR -4.83	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.8, phastCons 1
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00299% East Asian · 1/33,436 alleles

Filtering AF 0.000667% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000488%

Overall 0.00126% 15/1,190,654 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00299%	33,436
Admixed American	0.00224%	44,583
Remaining individualsnot grpmax-eligible	0.00214%	46,798
African / African-American	0.00177%	56,607
European (non-Finnish)	0.00124%	80,380

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.Arg565His
Coding: c.1694G>A
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs778779918
Type: single nucleotide variant
Location: chrX:101250576 (GRCh38)
Structure: AlphaFold pLDDT 90.49 · 15 PDB
Residue 565: a modified residue (asymmetric dimethylarginine)

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

Similar variants

DRP2 p.Arg565Cys Uncertain significance ★★ ⚠ same residue
DRP2 p.Arg565= Likely benign ★ 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

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-arg565his (accessed [today's date]).

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