Is DRP2 p.Ala205Val (c.614C>T) pathogenic?

DRP2 p.Ala205Val (c.614C>T) is classified Uncertain significance in DRP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-02). AlphaMissense: ambiguous (0.5428); Ultra-rare (popmax 0.0228%, mid).

How common is DRP2 p.Ala205Val (c.614C>T) in the general population?

DRP2 p.Ala205Val (c.614C>T) is ultra-rare (popmax 0.0228%, mid) (gnomAD).

What do computational predictors say about DRP2 p.Ala205Val (c.614C>T)?

AlphaMissense predicts ambiguous (score 0.5428) — an in-silico prediction, not a clinical call.

DRP2 p.Ala205Val

c.614C>T · rs755031248 · VCV2046222

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5428 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0228%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5428	ambiguous
REVEL	0.184	benign-leaning
SaProt	LLR -5.31	tolerated
⇒ REVEL and SaProt both call this tolerated; 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	24.7	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 0.0228% Middle Eastern · 1/4,377 alleles

Filtering AF 0.00284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00251%

Overall 0.00314% 38/1,209,818 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0228%	4,377
Remaining individualsnot grpmax-eligible	0.0042%	23,804
European (non-Finnish)	0.00391%	25,578

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.Ala205Val
Coding: c.614C>T
MANE Select: NM_001197293 · reported on NM_001939
dbSNP: rs755031248
Type: single nucleotide variant
Location: chrX:101241722 (GRCh38)
Structure: AlphaFold pLDDT 90.49 · 15 PDB
Residue 205: an α-helix

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

Similar variants

DRP2 p.Ala205Glu Uncertain significance ★ ⚠ same residue
DRP2 p.Ala205= 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.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-ala205val (accessed [today's date]).

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