Is DRP2 p.Leu197Phe (c.589C>T) pathogenic?

DRP2 p.Leu197Phe (c.589C>T) is classified Likely benign in DRP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-14). AlphaMissense: likely benign (0.1802); Ultra-rare (popmax 0.0159%, sas).

How common is DRP2 p.Leu197Phe (c.589C>T) in the general population?

DRP2 p.Leu197Phe (c.589C>T) is ultra-rare (popmax 0.0159%, sas) (gnomAD).

What do computational predictors say about DRP2 p.Leu197Phe (c.589C>T)?

AlphaMissense predicts likely benign (score 0.1802) — an in-silico prediction, not a clinical call.

DRP2 p.Leu197Phe

c.589C>T · rs772120737 · VCV1633221

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1802 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0159%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1802	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -7.84	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 2.9	GERP 0.77, phastCons 1
Overall
CADD	22.1	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 0.0159% South Asian · 9/56,780 alleles

Filtering AF 0.00823% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00617%

Overall 0.0038% 46/1,209,976 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0953%	1,049
South Asiangrpmax	0.0159%	6,309
Admixed American	0.00656%	15,254
Remaining individualsnot grpmax-eligible	0.0042%	23,810
European (non-Finnish)	0.00123%	81,382

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu197Phe
Coding: c.589C>T
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs772120737
Type: single nucleotide variant
Location: chrX:101241697 (GRCh38)
Structure: AlphaFold pLDDT 90.49 · 15 PDB
Residue 197: a β-strand

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

Similar variants

DRP2 p.Leu197= 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
DRP2 p.Arg199His Uncertain significance ★★ ⚠ same type
DRP2 p.Arg224Cys 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-leu197phe (accessed [today's date]).

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