Is DOCK7 p.Pro464= (c.1392A>G) pathogenic?

DOCK7 p.Pro464= (c.1392A>G) is classified Benign/Likely benign in DOCK7 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.79%, afr); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Pro464= (c.1392A>G)?

DOCK7 p.Pro464= (c.1392A>G) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Pro464= (c.1392A>G) in the general population?

DOCK7 p.Pro464= (c.1392A>G) is low-frequency (popmax 1.79%, afr) (gnomAD).

DOCK7 p.Pro464=

c.1392A>G · rs116172511 · VCV475126

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.79%, afr)

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 -0.29	GERP -4.5, phastCons 0.002
Overall
CADD	7.941	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.79% African / African-American · 1,347/75,044 alleles

Filtering AF 1.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.68%

Overall 0.0958% 1,547/1,614,036 alleles · low-frequency exomes 749/1,461,742 · genomes 798/152,294 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.79%	56
Admixed American	0.137%	732
Remaining individualsnot grpmax-eligible	0.128%	781
Middle Eastern	0.066%	1,515
South Asian	0.00439%	22,766
European (non-Finnish)	0.00254%	39,332

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.Pro464=
Coding: c.1392A>G
MANE Select: NM_001367561
dbSNP: rs116172511
Type: single nucleotide variant
Location: chr1:62625292 (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-pro464 (accessed [today's date]).

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