Is DRP2 p.Gln347Ter (c.1039C>T) pathogenic?

DRP2 p.Gln347Ter (c.1039C>T) is classified Uncertain significance in DRP2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-05). Very rare (popmax 0.000447%, nfe); Associated with Charcot-Marie-Tooth disease X-linked dominant 1.

What condition is associated with DRP2 p.Gln347Ter (c.1039C>T)?

DRP2 p.Gln347Ter (c.1039C>T) is associated with Charcot-Marie-Tooth disease X-linked dominant 1 (ClinVar).

How common is DRP2 p.Gln347Ter (c.1039C>T) in the general population?

DRP2 p.Gln347Ter (c.1039C>T) is very rare (popmax 0.000447%, nfe) (gnomAD).

How is X-linked Charcot-Marie-Tooth disease type 1 inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

DRP2 p.Gln347Ter

c.1039C>T · rs1057519071 · VCV372142

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000447%, nfe)

Conditions

Charcot-Marie-Tooth disease X-linked dominant 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	Δ0.27	donor loss · deltas
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000447% European (non-Finnish) · 4/895,070 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000455% 5/1,097,731 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0021%	47,613
European (non-Finnish)grpmax	0.000447%	223,768

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln347Ter
Coding: c.1039C>T
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs1057519071
Type: single nucleotide variant
Location: chrX:101242967 (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 X-linked dominant 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked Charcot-Marie-Tooth disease type 1 (Orphanet):

Inheritance: X-linked dominant
Onset: Childhood

Similar variants

DPYSL2 p.Ile347= Benign ★★ same residue
DRP2 p.Gln347His Uncertain significance ★ ⚠ same residue
DRP2 p.Gln222Ter Pathogenic ★ same condition
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

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-gln347ter (accessed [today's date]).

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