Is DRP2 p.Ser90Phe (c.269C>T) pathogenic?

DRP2 p.Ser90Phe (c.269C>T) is classified Uncertain significance in DRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-27). AlphaMissense: likely pathogenic (0.9536); Absent from gnomAD v4.1.

How common is DRP2 p.Ser90Phe (c.269C>T) in the general population?

DRP2 p.Ser90Phe (c.269C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DRP2 p.Ser90Phe (c.269C>T)?

AlphaMissense predicts likely pathogenic (score 0.9536) — an in-silico prediction, not a clinical call.

DRP2 p.Ser90Phe

c.269C>T · rs2147336048 · VCV2004190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9536 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9536	likely pathogenic
REVEL	0.398	indeterminate
SaProt	LLR -6.58	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 5.9	GERP 1.7, phastCons 1
Overall
CADD	25.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DRP2
Protein: p.Ser90Phe
Coding: c.269C>T
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs2147336048
Type: single nucleotide variant
Location: chrX:101236011 (GRCh38)
Structure: AlphaFold pLDDT 90.49 · 15 PDB
Residue 90: an α-helix

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

Similar variants

DRP2 p.Ser90Cys 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.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-ser90phe (accessed [today's date]).

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