Is DRP2 p.Arg417His (c.1250G>A) pathogenic?

DRP2 p.Arg417His (c.1250G>A) is classified Uncertain significance in DRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-08). AlphaMissense: likely benign (0.2778); Very rare (popmax 0.000224%, nfe).

How common is DRP2 p.Arg417His (c.1250G>A) in the general population?

DRP2 p.Arg417His (c.1250G>A) is very rare (popmax 0.000224%, nfe) (gnomAD).

What do computational predictors say about DRP2 p.Arg417His (c.1250G>A)?

AlphaMissense predicts likely benign (score 0.2778) — an in-silico prediction, not a clinical call.

DRP2 p.Arg417His

c.1250G>A · rs759825823 · VCV2914887

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2778 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000224%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2778	likely benign
REVEL	0.347	indeterminate
SaProt	LLR -5.75	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 12	GERP 1.8, phastCons 1
Overall
CADD	32.0	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 0.000224% European (non-Finnish) · 2/891,216 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000183% 2/1,092,040 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.Arg417His
Coding: c.1250G>A
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs759825823
Type: single nucleotide variant
Location: chrX:101247162 (GRCh38)
Structure: AlphaFold pLDDT 90.49 · 15 PDB
Residue 417: a β-strand

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

Similar variants

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
DRP2 p.Arg224His 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-arg417his (accessed [today's date]).

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