Is DRP2 p.Phe175Cys (c.524T>G) pathogenic?

DRP2 p.Phe175Cys (c.524T>G) is classified Benign in DRP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-30). AlphaMissense: likely pathogenic (0.7328); Low-frequency (popmax 1.75%, afr).

How common is DRP2 p.Phe175Cys (c.524T>G) in the general population?

DRP2 p.Phe175Cys (c.524T>G) is low-frequency (popmax 1.75%, afr) (gnomAD).

What do computational predictors say about DRP2 p.Phe175Cys (c.524T>G)?

AlphaMissense predicts likely pathogenic (score 0.7328) — an in-silico prediction, not a clinical call.

DRP2 p.Phe175Cys

c.524T>G · rs151085921 · VCV1601725

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7328 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.75%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7328	likely pathogenic
REVEL	0.352	indeterminate
SaProt	LLR -5.90	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1
Overall
CADD	25.0	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 1.75% African / African-American · 997/57,030 alleles

Filtering AF 1.66% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.62%

Overall 0.0928% 1,122/1,209,101 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.75%	57
Remaining individualsnot grpmax-eligible	0.124%	806
Admixed American	0.0875%	1,142
Middle Eastern	0.0231%	4,322
South Asian	0.00706%	14,158
European (non-Finnish)	0.00235%	42,613

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.Phe175Cys
Coding: c.524T>G
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs151085921
Type: single nucleotide variant
Location: chrX:101239066 (GRCh38)
Structure: AlphaFold pLDDT 90.49 · 15 PDB
Residue 175: an α-helix

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-phe175cys (accessed [today's date]).

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