Is DOCK7 p.Glu148fs (c.443_446del) pathogenic?

DOCK7 p.Glu148fs (c.443446del) is classified Pathogenic/Likely pathogenic in DOCK7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-14). Very rare (popmax 0.000442%, nfe); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Glu148fs (c.443_446del)?

DOCK7 p.Glu148fs (c.443_446del) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Glu148fs (c.443_446del) in the general population?

DOCK7 p.Glu148fs (c.443_446del) is very rare (popmax 0.000442%, nfe) (gnomAD).

DOCK7 p.Glu148fs

c.443_446del · rs1438270423 · VCV1453674

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000442%, nfe)

Conditions

developmental and epileptic encephalopathy, 23

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 5 of 50
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -1.2, phastCons 1
Overall
CADD	33.0	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 0.000442% European (non-Finnish) · 5/1,130,194 alleles

Filtering AF 0.00013% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.4e-05%

Overall 0.000328% 5/1,523,956 alleles · very 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: DOCK7
Protein: p.Glu148fs
Coding: c.443_446del
MANE Select: NM_001367561
dbSNP: rs1438270423
Type: Microsatellite
Location: chr1:62648488 (GRCh38)
Gene constraint: LOEUF 0.551 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 2 PDB
Residue 148: the 'disordered' region

Full DOCK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 23 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK7 p.Glu148= Likely benign ★ same residue
DOCK7 c.3612-18CTT[2] Likely benign ★★ same condition
DOCK7 p.Met1448fs Pathogenic ★ same condition
DOCK7 p.Pro1946fs Pathogenic ★ same condition
DOCK7 p.Pro703fs Pathogenic ★ same condition
DOCK7 p.Lys10del Uncertain significance ★ same condition
DOCK7 p.Ser12del Uncertain significance ★ same condition
DOCK7 p.Ser864del Uncertain significance ★ same condition

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/dock7-p-glu148fs (accessed [today's date]).

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