Is DOCK7 p.Arg77Gln (c.230G>A) pathogenic?

DOCK7 p.Arg77Gln (c.230G>A) is classified Uncertain significance in DOCK7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-10-03). AlphaMissense: likely benign (0.1254); Ultra-rare (popmax 0.0549%, sas); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Arg77Gln (c.230G>A)?

DOCK7 p.Arg77Gln (c.230G>A) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Arg77Gln (c.230G>A) in the general population?

DOCK7 p.Arg77Gln (c.230G>A) is ultra-rare (popmax 0.0549%, sas) (gnomAD).

What do computational predictors say about DOCK7 p.Arg77Gln (c.230G>A)?

AlphaMissense predicts likely benign (score 0.1254) — an in-silico prediction, not a clinical call.

DOCK7 p.Arg77Gln

c.230G>A · rs376620846 · VCV641400

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1254 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 23

Computational evidence

Protein change
AlphaMissense	0.1254	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 175 kb · p 3.6e-10 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0549% South Asian · 50/91,062 alleles

Filtering AF 0.0427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0385%

Overall 0.00428% 69/1,613,884 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0549%	1,821
East Asian	0.00892%	11,215
Remaining individualsnot grpmax-eligible	0.0048%	20,836
African / African-American	0.00267%	37,504
Finnishnot grpmax-eligible	0.00156%	63,994
European (non-Finnish)	0.000763%	131,101

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.Arg77Gln
Coding: c.230G>A
MANE Select: NM_001367561
dbSNP: rs376620846
Type: single nucleotide variant
Location: chr1:62654074 (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.Arg77Trp Uncertain significance ★ ⚠ same residue
DOCK7 p.Arg77= Likely benign ★ 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

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-arg77gln (accessed [today's date]).

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