Is DOCK7 p.Glu987Lys (c.2959G>A) pathogenic?

DOCK7 p.Glu987Lys (c.2959G>A) is classified Uncertain significance in DOCK7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-02). AlphaMissense: likely pathogenic (0.9845); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with DOCK7 p.Glu987Lys (c.2959G>A)?

DOCK7 p.Glu987Lys (c.2959G>A) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Glu987Lys (c.2959G>A) in the general population?

DOCK7 p.Glu987Lys (c.2959G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DOCK7 p.Glu987Lys (c.2959G>A)?

AlphaMissense predicts likely pathogenic (score 0.9845) — an in-silico prediction, not a clinical call.

DOCK7 p.Glu987Lys

c.2959G>A · rs540487612 · VCV653019

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9845	likely pathogenic
REVEL	0.458	indeterminate
SaProt	LLR -11.53	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 175 kb · p 3.6e-10 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00167% Admixed American · 1/59,874 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000372% 6/1,612,536 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,874
African / African-American	0.00133%	74,942
European (non-Finnish)	0.000339%	294,810

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.Glu987Lys
Coding: c.2959G>A
MANE Select: NM_001367561
dbSNP: rs540487612
Type: single nucleotide variant
Location: chr1:62542694 (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.Glu987Val Uncertain significance ★ ⚠ same residue
DOCK7 p.Glu987= 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-glu987lys (accessed [today's date]).

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