Is DOCK7 p.Ala1004Pro (c.3010G>C) pathogenic?

DOCK7 p.Ala1004Pro (c.3010G>C) is classified Uncertain significance in DOCK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-19). AlphaMissense: likely pathogenic (0.9909); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Ala1004Pro (c.3010G>C)?

DOCK7 p.Ala1004Pro (c.3010G>C) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Ala1004Pro (c.3010G>C) in the general population?

DOCK7 p.Ala1004Pro (c.3010G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOCK7 p.Ala1004Pro (c.3010G>C)?

AlphaMissense predicts likely pathogenic (score 0.9909) — an in-silico prediction, not a clinical call.

DOCK7 p.Ala1004Pro

c.3010G>C · VCV3694650

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9909 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

developmental and epileptic encephalopathy, 23

Computational evidence

Protein change
AlphaMissense	0.9909	likely pathogenic · top 9% in DOCK7
REVEL	0.54	indeterminate
SaProt	LLR -12.79	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	26.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DOCK7
Protein: p.Ala1004Pro
Coding: c.3010G>C
MANE Select: NM_001367561
Type: single nucleotide variant
Location: chr1:62542643 (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 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
DOCK7 p.Ala1479Thr 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-ala1004pro (accessed [today's date]).

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