Is DRP2 p.Ser744Phe (c.2231C>T) pathogenic?

DRP2 p.Ser744Phe (c.2231C>T) is classified Uncertain significance in DRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-10). AlphaMissense: ambiguous (0.4822); Ultra-rare (popmax 0.023%, mid).

How common is DRP2 p.Ser744Phe (c.2231C>T) in the general population?

DRP2 p.Ser744Phe (c.2231C>T) is ultra-rare (popmax 0.023%, mid) (gnomAD).

What do computational predictors say about DRP2 p.Ser744Phe (c.2231C>T)?

AlphaMissense predicts ambiguous (score 0.4822) — an in-silico prediction, not a clinical call.

DRP2 p.Ser744Phe

c.2231C>T · VCV3713494

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4822 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4822	ambiguous
REVEL	0.747	pathogenic-leaning
SaProt	LLR -7.98	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Overall
CADD	24.9	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 0.023% Middle Eastern · 1/4,350 alleles

Filtering AF 0.0014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000689%

Overall 0.00116% 14/1,208,627 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.023%	4,350
Remaining individualsnot grpmax-eligible	0.0063%	15,861
South Asian	0.00529%	18,902
European (non-Finnish)	0.000783%	127,758

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.Ser744Phe
Coding: c.2231C>T
MANE Select: NM_001197293 · reported on NM_001939
Type: single nucleotide variant
Location: chrX:101255234 (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.Ser744Tyr Uncertain significance ★ ⚠ same residue
DRP2 p.Ser744= 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

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-ser744phe (accessed [today's date]).

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