Is DRP2 p.Arg199His (c.596G>A) pathogenic?

DRP2 p.Arg199His (c.596G>A) is classified Uncertain significance in DRP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-07). AlphaMissense: likely benign (0.1935); Very rare (popmax 0.00888%, eas).

How common is DRP2 p.Arg199His (c.596G>A) in the general population?

DRP2 p.Arg199His (c.596G>A) is very rare (popmax 0.00888%, eas) (gnomAD).

What do computational predictors say about DRP2 p.Arg199His (c.596G>A)?

AlphaMissense predicts likely benign (score 0.1935) — an in-silico prediction, not a clinical call.

DRP2 p.Arg199His

c.596G>A · rs753921064 · VCV2416748

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1935 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00888%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1935	likely benign
REVEL	0.457	indeterminate
SaProt	LLR -7.52	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00888% East Asian · 3/33,777 alleles

Filtering AF 0.00235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00125%

Overall 0.00107% 13/1,209,870 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00888%	11,259
South Asian	0.00352%	28,401
Finnishnot grpmax-eligible	0.00215%	46,523
African / African-American	0.00175%	57,101
European (non-Finnish)	0.00067%	149,206

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.Arg199His
Coding: c.596G>A
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs753921064
Type: single nucleotide variant
Location: chrX:101241704 (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.Arg199Cys Uncertain significance ★ ⚠ 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.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-arg199his (accessed [today's date]).

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