Is DRP2 p.Ser60Arg (c.180C>A) pathogenic?

DRP2 p.Ser60Arg (c.180C>A) is classified Benign in DRP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1928); Low-frequency (popmax 2.22%, mid).

How common is DRP2 p.Ser60Arg (c.180C>A) in the general population?

DRP2 p.Ser60Arg (c.180C>A) is low-frequency (popmax 2.22%, mid) (gnomAD).

What do computational predictors say about DRP2 p.Ser60Arg (c.180C>A)?

AlphaMissense predicts likely benign (score 0.1928) — an in-silico prediction, not a clinical call.

DRP2 p.Ser60Arg

c.180C>A · rs34013624 · VCV1607655

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1928 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.22%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1928	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -7.06	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 -0.29	GERP -1.4, phastCons 0.21
Overall
CADD	12.61	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 2.22% Middle Eastern · 96/4,326 alleles

Filtering AF 1.86% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.73%

Overall 1.35% 16,379/1,210,319 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.22%	45
Finnishnot grpmax-eligible	2.05%	49
Ashkenazi Jewishnot grpmax-eligible	1.5%	67
European (non-Finnish)	1.49%	67
South Asian	1.47%	68
Remaining individualsnot grpmax-eligible	1.21%	83
Admixed American	0.279%	358
African / African-American	0.162%	616
East Asian	0.0207%	4,825

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.Ser60Arg
Coding: c.180C>A
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs34013624
Type: single nucleotide variant
Location: chrX:101235922 (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-ser60arg (accessed [today's date]).

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