Is DOCK7 p.Ser728= (c.2184G>A) pathogenic?

DOCK7 p.Ser728= (c.2184G>A) is classified Likely benign in DOCK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-23). Very rare (popmax 0.00997%, nfe); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Ser728= (c.2184G>A)?

DOCK7 p.Ser728= (c.2184G>A) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Ser728= (c.2184G>A) in the general population?

DOCK7 p.Ser728= (c.2184G>A) is very rare (popmax 0.00997%, nfe) (gnomAD).

DOCK7 p.Ser728=

c.2184G>A · rs769422184 · VCV541928

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00997%, nfe)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.1	GERP -4, phastCons 0.98
Overall
CADD	14.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00997% European (non-Finnish) · 116/1,163,002 alleles

Filtering AF 0.00846% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00788%

Overall 0.0078% 122/1,563,802 alleles · very rare exomes 117/1,411,864 · genomes 5/151,938 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00997%	10,026
Remaining individualsnot grpmax-eligible	0.00497%	20,117
Finnishnot grpmax-eligible	0.00159%	63,086
African / African-American	0.00139%	71,864
South Asian	0.00125%	80,028

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.Ser728=
Coding: c.2184G>A
MANE Select: NM_001367561
dbSNP: rs769422184
Type: single nucleotide variant
Location: chr1:62561632 (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 c.4924-1G>A Pathogenic/Likely pathogenic ★★ same condition
DOCK7 p.Arg1380Ter Pathogenic ★★ same condition
DOCK7 p.Arg1415Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK7 p.Arg429Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK7 p.Arg445Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK7 c.3781+4C>G Uncertain significance ★★ same condition
DOCK7 c.38+6T>C Uncertain significance ★★ same condition
DOCK7 p.Ala1479Thr 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-ser728 (accessed [today's date]).

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