Is DRP2 p.His440= (c.1320C>T) pathogenic?

DRP2 p.His440= (c.1320C>T) is classified Likely benign in DRP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-30). Ultra-rare (popmax 0.0372%, amr).

How common is DRP2 p.His440= (c.1320C>T) in the general population?

DRP2 p.His440= (c.1320C>T) is ultra-rare (popmax 0.0372%, amr) (gnomAD).

DRP2 p.His440=

c.1320C>T · rs146293556 · VCV760767

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0372%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -3.7
Overall
CADD	2.618	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0372% Admixed American · 17/45,721 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0194%

Overall 0.00248% 30/1,209,784 alleles · ultra-rare exomes 28/1,098,024 · genomes 2/111,760 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0372%	2,689
Remaining individualsnot grpmax-eligible	0.0042%	23,803
South Asian	0.00352%	28,385
African / African-American	0.0035%	28,581
European (non-Finnish)	0.000782%	127,873

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.His440=
Coding: c.1320C>T
MANE Select: NM_001939
dbSNP: rs146293556
Type: single nucleotide variant
Location: chrX:101248156 (GRCh38)
Structure: AlphaFold pLDDT 90.49 · 15 PDB
Residue 440: a β-strand

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

Similar variants

DPYSL2 p.Thr440Met 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-his440 (accessed [today's date]).

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