Is DOCK7 p.Ser1786Phe (c.5357C>T) pathogenic?

DOCK7 p.Ser1786Phe (c.5357C>T) is classified Uncertain significance in DOCK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: ambiguous (0.4279); Very rare (popmax 0.00167%, amr); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Ser1786Phe (c.5357C>T)?

DOCK7 p.Ser1786Phe (c.5357C>T) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Ser1786Phe (c.5357C>T) in the general population?

DOCK7 p.Ser1786Phe (c.5357C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DOCK7 p.Ser1786Phe (c.5357C>T)?

AlphaMissense predicts ambiguous (score 0.4279) — an in-silico prediction, not a clinical call.

DOCK7 p.Ser1786Phe

c.5357C>T · rs764567672 · VCV1039295

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4279 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

developmental and epileptic encephalopathy, 23

Computational evidence

Protein change
AlphaMissense	0.4279	ambiguous
REVEL	0.328	indeterminate
SaProt	LLR -8.29	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 58 kb · p 5.9e-19 · regional, not allelic
Overall
CADD	27.6	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 0.00167% Admixed American · 1/60,012 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,738 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,012
European (non-Finnish)	0.000169%	589,977

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.Ser1786Phe
Coding: c.5357C>T
MANE Select: NM_001367561
dbSNP: rs764567672
Type: single nucleotide variant
Location: chr1:62492708 (GRCh38)
Gene constraint: LOEUF 0.551 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 2 PDB
Residue 1786: the docker domain

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.Ser1786Pro 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-ser1786phe (accessed [today's date]).

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