Is DOCK7 p.Arg2127= (c.6381A>G) pathogenic?

DOCK7 p.Arg2127= (c.6381A>G) is classified Conflicting classifications of pathogenicity in DOCK7 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-02). Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with DOCK7 p.Arg2127= (c.6381A>G)?

DOCK7 p.Arg2127= (c.6381A>G) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Arg2127= (c.6381A>G) in the general population?

DOCK7 p.Arg2127= (c.6381A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

DOCK7 p.Arg2127=

c.6381A>G · rs1166858046 · VCV848643

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.087	moderately benign-leaning
Splicing
SpliceAI	Δ0.72	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.9	GERP 0.23, phastCons 1
Overall
CADD	13.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,892 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00105% 17/1,613,296 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,446
Remaining individualsnot grpmax-eligible	0.0016%	62,456
European (non-Finnish)	0.00119%	84,262

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.Arg2127=
Coding: c.6381A>G
MANE Select: NM_001367561
dbSNP: rs1166858046
Type: single nucleotide variant
Location: chr1:62455456 (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.Arg2127Lys 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-arg2127 (accessed [today's date]).

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