Is DRP2 p.Ser29fs (c.86del) pathogenic?

DRP2 p.Ser29fs (c.86del) is classified Uncertain significance in DRP2 (ClinVar, No assertion criteria, 2 submitters). Very rare (popmax 0.000447%, nfe).

How common is DRP2 p.Ser29fs (c.86del) in the general population?

DRP2 p.Ser29fs (c.86del) is very rare (popmax 0.000447%, nfe) (gnomAD).

DRP2 p.Ser29fs

c.86del · rs2147332623 · VCV1297513

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000447%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP 0.49, phastCons 0.95

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) · 4/895,163 alleles

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

Overall 0.000364% 4/1,097,863 alleles · very rare

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.Ser29fs
Coding: c.86del
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs2147332623
Type: Deletion
Location: chrX:101231733 (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 c.1677_1698+44del Likely pathogenic ★ same type
DRP2 p.Ala127fs Likely pathogenic ★ same type
DRP2 p.Glu838fs Pathogenic ★ same type
DRP2 p.Phe769fs Pathogenic ★ same type
DRP2 p.Pro174fs Pathogenic ★ same type
DRP2 p.Ser776fs Pathogenic ★ same type
DPYSL2 p.Ala405fs Uncertain significance ★ same type
DPYSL2 p.Gly91fs 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-ser29fs (accessed [today's date]).

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