Is DOCK7 p.Phe2130Cys (c.6389T>G) pathogenic?

DOCK7 p.Phe2130Cys (c.6389T>G) is classified Uncertain significance in DOCK7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-06). AlphaMissense: ambiguous (0.3542); Very rare (popmax 8.48e-05%, nfe); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Phe2130Cys (c.6389T>G)?

DOCK7 p.Phe2130Cys (c.6389T>G) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Phe2130Cys (c.6389T>G) in the general population?

DOCK7 p.Phe2130Cys (c.6389T>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DOCK7 p.Phe2130Cys (c.6389T>G)?

AlphaMissense predicts ambiguous (score 0.3542) — an in-silico prediction, not a clinical call.

DOCK7 p.Phe2130Cys

c.6389T>G · rs1645319931 · VCV1474836

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3542 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

developmental and epileptic encephalopathy, 23

Computational evidence

Protein change
AlphaMissense	0.3542	ambiguous
REVEL	0.441	indeterminate
SaProt	LLR -7.12	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 58 kb · p 5.9e-19 · regional, not allelic
Overall
CADD	26.9	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 8.48e-05% European (non-Finnish) · 1/1,179,782 alleles

Overall 6.84e-05% 1/1,461,328 alleles · very rare

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.Phe2130Cys
Coding: c.6389T>G
MANE Select: NM_001367561
dbSNP: rs1645319931
Type: single nucleotide variant
Location: chr1:62455448 (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-phe2130cys (accessed [today's date]).

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