Is DOCK7 p.Ser12del (c.33CAG[1]) pathogenic?

DOCK7 p.Ser12del (c.33CAG[1]) is classified Uncertain significance in DOCK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-12). Very rare (popmax 0.00531%, amr); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Ser12del (c.33CAG[1])?

DOCK7 p.Ser12del (c.33CAG[1]) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Ser12del (c.33CAG[1]) in the general population?

DOCK7 p.Ser12del (c.33CAG[1]) is very rare (popmax 0.00531%, amr) (gnomAD).

DOCK7 p.Ser12del

c.33CAG[1] · rs1219264955 · VCV1036362

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00531%, amr)

Conditions

developmental and epileptic encephalopathy, 23

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 6.3	GERP 0.96, phastCons 1
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00531% Admixed American · 2/37,662 alleles

Filtering AF 0.00088% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000329%

Overall 0.00029% 4/1,378,750 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00531%	18,831
Remaining individualsnot grpmax-eligible	0.00197%	50,638
European (non-Finnish)	9.49e-05%	1,053,922

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.Ser12del
Coding: c.33CAG[1]
MANE Select: NM_001367561
dbSNP: rs1219264955
Type: Microsatellite
Location: chr1:62688227 (GRCh38)
Gene constraint: LOEUF 0.551 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 2 PDB

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.Glu148fs Pathogenic/Likely pathogenic ★★ same condition
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.Ser864del Uncertain significance ★ same condition
DOCK7 c.520-22_520-17del Likely benign ★ 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-ser12del (accessed [today's date]).

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