Is DPH1 p.Glu305fs (c.914_927del) pathogenic?

DPH1 p.Glu305fs (c.914927del) is classified Pathogenic in DPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-30). Ultra-rare (popmax 0.0111%, eas).

How common is DPH1 p.Glu305fs (c.914_927del) in the general population?

DPH1 p.Glu305fs (c.914_927del) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

DPH1 p.Glu305fs

c.914_927del · rs757405584 · VCV1188796

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,884 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00031% 5/1,614,190 alleles · ultra-rare

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.Glu305fs
Coding: c.914_927del
MANE Select: NM_001383
dbSNP: rs757405584
Type: Deletion
Location: chr17:2040512 (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.Glu92fs Pathogenic/Likely pathogenic ★★ same type
DPH1 p.Tyr263del Uncertain significance ★★ same type
DPH1 p.Arg153fs Likely pathogenic ★ same type
DPH1 p.Pro169fs Likely pathogenic ★ same type
DPH1 p.His400fs Uncertain significance ★ same type
DPH1 p.Met268del Uncertain significance ★ same type
DPH1 p.Pro217del 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-glu305fs (accessed [today's date]).

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