Is DRP2 p.Val68Leu (c.202G>C) pathogenic?

DRP2 p.Val68Leu (c.202G>C) is classified Benign in DRP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0866); Common (popmax 18.3%, mid) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DRP2 p.Val68Leu (c.202G>C)?

AlphaMissense predicts likely benign (score 0.0866) — an in-silico prediction, not a clinical call.

DRP2 p.Val68Leu

Q: How common is DRP2 p.Val68Leu (c.202G>C) in the general population?

DRP2 p.Val68Leu (c.202G>C) is common (popmax 18.3%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.202G>C · rs7066252 · VCV1610826

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0866 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 18.3%, mid) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0866	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -5.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -3
Overall
CADD	1.292	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 18.3% Middle Eastern · 795/4,341 alleles

Filtering AF 17.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.8%

Overall 12.6% 152,262/1,209,916 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	18.3%	5
Ashkenazi Jewishnot grpmax-eligible	14.7%	7
African / African-American	13.9%	7
European (non-Finnish)	13.4%	7
Remaining individualsnot grpmax-eligible	13%	8
Admixed American	10.8%	9
Finnishnot grpmax-eligible	8.53%	12
East Asian	6.16%	16
Amishnot grpmax-eligible	5.69%	18
South Asian	4.81%	21

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.Val68Leu
Coding: c.202G>C
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs7066252
Type: single nucleotide variant
Location: chrX:101235944 (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.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
DRP2 p.Arg224His 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-val68leu (accessed [today's date]).

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