Is DRP2 p.Arg492Gln (c.1475G>A) pathogenic?

DRP2 p.Arg492Gln (c.1475G>A) is classified Uncertain significance in DRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-26). AlphaMissense: likely benign (0.2527); Very rare (popmax 0.00296%, eas).

How common is DRP2 p.Arg492Gln (c.1475G>A) in the general population?

DRP2 p.Arg492Gln (c.1475G>A) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about DRP2 p.Arg492Gln (c.1475G>A)?

AlphaMissense predicts likely benign (score 0.2527) — an in-silico prediction, not a clinical call.

DRP2 p.Arg492Gln

c.1475G>A · VCV3620379

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2527 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2527	likely benign
REVEL	0.641	indeterminate
SaProt	LLR -10.73	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00296% East Asian · 1/33,791 alleles

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

Overall 0.000248% 3/1,210,205 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00296%	33,791
European (non-Finnish)	0.000223%	447,622

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.Arg492Gln
Coding: c.1475G>A
MANE Select: NM_001197293 · reported on NM_001939
Type: single nucleotide variant
Location: chrX:101248534 (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.Asn492Ser Uncertain significance ★★ ⚠ same residue
DPYSL2 p.Asn492Ile Uncertain significance ★ ⚠ same residue
DRP2 p.Arg492= Likely benign ★ same residue
DRP2 p.Glu432Ter Pathogenic ★★ 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-arg492gln (accessed [today's date]).

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