Is DOCK7 p.Arg1380Gln (c.4139G>A) pathogenic?

DOCK7 p.Arg1380Gln (c.4139G>A) is classified Uncertain significance in DOCK7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-30). AlphaMissense: ambiguous (0.4745); Very rare (popmax 0.00535%, afr); Associated with Inborn genetic diseases.

What condition is associated with DOCK7 p.Arg1380Gln (c.4139G>A)?

DOCK7 p.Arg1380Gln (c.4139G>A) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Arg1380Gln (c.4139G>A) in the general population?

DOCK7 p.Arg1380Gln (c.4139G>A) is very rare (popmax 0.00535%, afr) (gnomAD).

What do computational predictors say about DOCK7 p.Arg1380Gln (c.4139G>A)?

AlphaMissense predicts ambiguous (score 0.4745) — an in-silico prediction, not a clinical call.

DOCK7 p.Arg1380Gln

c.4139G>A · rs368205214 · VCV581308

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4745 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4745	ambiguous
REVEL	0.243	benign-leaning
SaProt	LLR -6.91	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 58 kb · p 5.9e-19 · regional, not allelic
Overall
CADD	29.5	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 0.00535% African / African-American · 4/74,790 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00391% 63/1,612,312 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00641%	15,596
African / African-Americangrpmax	0.00535%	18,697
European (non-Finnish)	0.00449%	22,258
East Asian	0.00223%	44,892
Admixed American	0.00168%	59,512

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg1380Gln
Coding: c.4139G>A
MANE Select: NM_001367561
dbSNP: rs368205214
Type: single nucleotide variant
Location: chr1:62513587 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 23

Similar variants

DOCK7 p.Arg1380Ter Pathogenic ★★ same residue
DOCK7 p.Arg1380Pro Uncertain significance ★ ⚠ same residue
DOCK7 c.4924-1G>A Pathogenic/Likely 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-arg1380gln (accessed [today's date]).

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