Is DRP2 p.Arg945Ter (c.2833C>T) pathogenic?

DRP2 p.Arg945Ter (c.2833C>T) is classified Uncertain significance in DRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). Very rare (popmax 0.00217%, amr).

How common is DRP2 p.Arg945Ter (c.2833C>T) in the general population?

DRP2 p.Arg945Ter (c.2833C>T) is very rare (popmax 0.00217%, amr) (gnomAD).

DRP2 p.Arg945Ter

c.2833C>T · rs1259322036 · VCV1909357

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00217%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.79	GERP -1.8, phastCons 0.74
Overall
CADD	35.0	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 0.00217% Admixed American · 1/45,980 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000455% 5/1,097,704 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00217%	45,980
Remaining individualsnot grpmax-eligible	0.0021%	47,622
European (non-Finnish)	0.000335%	298,437

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.Arg945Ter
Coding: c.2833C>T
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs1259322036
Type: single nucleotide variant
Location: chrX:101260580 (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.Arg945Gln Uncertain significance ★ ⚠ same residue
DRP2 p.Arg945= Likely benign ★ 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

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-arg945ter (accessed [today's date]).

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