Is DPH1 p.Pro217del (c.650_652del) pathogenic?

DPH1 p.Pro217del (c.650652del) is classified Uncertain significance in DPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). Very rare (popmax 8.48e-05%, nfe).

How common is DPH1 p.Pro217del (c.650_652del) in the general population?

DPH1 p.Pro217del (c.650_652del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

DPH1 p.Pro217del

c.650_652del · VCV4755943

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.5	GERP 0.33, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,922 alleles

Overall 6.2e-05% 1/1,613,558 alleles · very rare exomes 1/1,461,452 · genomes 0/152,106 · joint denominator

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: DPH1
Protein: p.Pro217del
Coding: c.650_652del
MANE Select: NM_001383
Type: Deletion
Location: chr17:2036923 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.00

Full DPH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPH1 p.Pro217His Uncertain significance ★ same residue
DPH1 p.Glu92fs Pathogenic/Likely pathogenic ★★ same type
DPH1 p.Tyr263del Uncertain significance ★★ same type
DPH1 p.Arg153fs Likely pathogenic ★ same type
DPH1 p.Glu305fs Pathogenic ★ same type
DPH1 p.Pro169fs Likely pathogenic ★ same type
DPH1 p.His400fs Uncertain significance ★ same type
DPH1 p.Met268del 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/dph1-p-pro217del (accessed [today's date]).

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