Is DRP2 p.Arg720Gln (c.2159G>A) pathogenic?

DRP2 p.Arg720Gln (c.2159G>A) is classified Uncertain significance in DRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-21). AlphaMissense: likely benign (0.1796); Very rare (popmax 0.00175%, sas); Associated with Charcot-Marie-Tooth disease type X.

What condition is associated with DRP2 p.Arg720Gln (c.2159G>A)?

DRP2 p.Arg720Gln (c.2159G>A) is associated with Charcot-Marie-Tooth disease type X (ClinVar).

How common is DRP2 p.Arg720Gln (c.2159G>A) in the general population?

DRP2 p.Arg720Gln (c.2159G>A) is very rare (popmax 0.00175%, sas) (gnomAD).

What do computational predictors say about DRP2 p.Arg720Gln (c.2159G>A)?

AlphaMissense predicts likely benign (score 0.1796) — an in-silico prediction, not a clinical call.

DRP2 p.Arg720Gln

c.2159G>A · rs758462829 · VCV1802194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1796 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00175%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type X

Computational evidence

Protein change
AlphaMissense	0.1796	likely benign
REVEL	0.759	pathogenic-leaning
SaProt	LLR -7.46	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.22	donor loss · deltas
Pangolin	Δ0.24	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Overall
CADD	26.0	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 0.00175% South Asian · 1/56,982 alleles

Filtering AF 0.00101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000797%

Overall 0.00146% 16/1,098,243 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00175%	56,982
European (non-Finnish)	0.00167%	59,703

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.Arg720Gln
Coding: c.2159G>A
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs758462829
Type: single nucleotide variant
Location: chrX:101254903 (GRCh38)
Structure: AlphaFold pLDDT 90.49 · 15 PDB

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

Disease context

Charcot-Marie-Tooth disease type X — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DRP2 p.Arg720Ter Pathogenic ★ 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-arg720gln (accessed [today's date]).

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