Is DOCK7 p.Arg760Gln (c.2279G>A) pathogenic?

DOCK7 p.Arg760Gln (c.2279G>A) is classified Uncertain significance in DOCK7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-04-11). AlphaMissense: ambiguous (0.3968); Very rare (popmax 0.00334%, amr); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Arg760Gln (c.2279G>A)?

DOCK7 p.Arg760Gln (c.2279G>A) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Arg760Gln (c.2279G>A) in the general population?

DOCK7 p.Arg760Gln (c.2279G>A) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about DOCK7 p.Arg760Gln (c.2279G>A)?

AlphaMissense predicts ambiguous (score 0.3968) — an in-silico prediction, not a clinical call.

DOCK7 p.Arg760Gln

c.2279G>A · rs775510896 · VCV445964

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3968 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

developmental and epileptic encephalopathy, 23

Computational evidence

Protein change
AlphaMissense	0.3968	ambiguous
REVEL	0.297	indeterminate
SaProt	LLR -1.50	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 175 kb · p 3.6e-10 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,902 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000372% 6/1,613,614 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,951
African / African-American	0.00267%	37,440
Remaining individualsnot grpmax-eligible	0.0016%	62,464
European (non-Finnish)	8.48e-05%	1,179,880

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.Arg760Gln
Coding: c.2279G>A
MANE Select: NM_001367561
dbSNP: rs775510896
Type: single nucleotide variant
Location: chr1:62559141 (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.Arg760Ter Pathogenic ★ 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-arg760gln (accessed [today's date]).

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