Is DRP2 p.Leu503= (c.1509G>A) pathogenic?

DRP2 p.Leu503= (c.1509G>A) is classified Likely benign in DRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-09). Very rare (popmax 0.0088%, sas).

How common is DRP2 p.Leu503= (c.1509G>A) in the general population?

DRP2 p.Leu503= (c.1509G>A) is very rare (popmax 0.0088%, sas) (gnomAD).

DRP2 p.Leu503=

c.1509G>A · rs149294275 · VCV1544531

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0088%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.75	GERP -0.54, phastCons 1
Overall
CADD	4.587	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0088% South Asian · 5/56,834 alleles

Filtering AF 0.00497% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00454%

Overall 0.00512% 62/1,210,774 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0088%	11,367
European (non-Finnish)	0.00637%	15,708

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.Leu503=
Coding: c.1509G>A
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs149294275
Type: single nucleotide variant
Location: chrX:101248568 (GRCh38)
Structure: AlphaFold pLDDT 90.49 · 15 PDB

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

Similar variants

DPYSL2 p.Lys503Arg Uncertain significance ★ ⚠ same residue
DRP2 p.Leu503Phe Uncertain significance ★ ⚠ same residue
DPYSL2 p.Lys503= 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

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-leu503 (accessed [today's date]).

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