Is DOCK7 p.Arg463= (c.1389A>C) pathogenic?

DOCK7 p.Arg463= (c.1389A>C) is classified Benign in DOCK7 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 6.25%, afr) — too common for a highly-penetrant pathogenic allele; Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Arg463= (c.1389A>C)?

DOCK7 p.Arg463= (c.1389A>C) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

DOCK7 p.Arg463=

Q: How common is DOCK7 p.Arg463= (c.1389A>C) in the general population?

DOCK7 p.Arg463= (c.1389A>C) is common (popmax 6.25%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1389A>C · rs35627175 · VCV475125

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 6.25%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.2	GERP -4.3, phastCons 0.64
Overall
CADD	7.567	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.25% African / African-American · 4,692/75,022 alleles

Filtering AF 6.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.04%

Overall 0.338% 5,451/1,614,002 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.25%	16
Admixed American	0.487%	206
Remaining individualsnot grpmax-eligible	0.477%	210
Middle Eastern	0.149%	673
European (non-Finnish)	0.0127%	7,867
South Asian	0.011%	9,106

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.Arg463=
Coding: c.1389A>C
MANE Select: NM_001367561
dbSNP: rs35627175
Type: single nucleotide variant
Location: chr1:62625295 (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.Arg463Gln Uncertain significance ★ ⚠ same residue
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

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-arg463 (accessed [today's date]).

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