Is DRP2 p.Arg543His (c.1628G>A) pathogenic?

DRP2 p.Arg543His (c.1628G>A) is classified Uncertain significance in DRP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-02). AlphaMissense: ambiguous (0.4659); Very rare (popmax 0.00296%, eas).

How common is DRP2 p.Arg543His (c.1628G>A) in the general population?

DRP2 p.Arg543His (c.1628G>A) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about DRP2 p.Arg543His (c.1628G>A)?

AlphaMissense predicts ambiguous (score 0.4659) — an in-silico prediction, not a clinical call.

DRP2 p.Arg543His

c.1628G>A · rs779675953 · VCV2595777

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4659 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4659	ambiguous
REVEL	0.775	moderately pathogenic-leaning
SaProt	LLR -13.49	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense 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

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 · 1/33,799 alleles

Filtering AF 0.000384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000278%

Overall 0.000911% 10/1,097,436 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00296%	33,799
African / African-American	0.00174%	57,602
European (non-Finnish)	0.000894%	111,878

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.Arg543His
Coding: c.1628G>A
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs779675953
Type: single nucleotide variant
Location: chrX:101250510 (GRCh38)
Structure: AlphaFold pLDDT 90.49 · 15 PDB

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-arg543his (accessed [today's date]).

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