Is DOCK7 p.Phe648= (c.1944T>C) pathogenic?

DOCK7 p.Phe648= (c.1944T>C) is classified Likely benign in DOCK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). Ultra-rare (popmax 0.0353%, amr); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Phe648= (c.1944T>C)?

DOCK7 p.Phe648= (c.1944T>C) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Phe648= (c.1944T>C) in the general population?

DOCK7 p.Phe648= (c.1944T>C) is ultra-rare (popmax 0.0353%, amr) (gnomAD).

DOCK7 p.Phe648=

c.1944T>C · rs199869677 · VCV770099

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0353%, amr)

Conditions

developmental and epileptic encephalopathy, 23

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP -0.42, phastCons 1
Overall
CADD	12.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0353% Admixed American · 21/59,408 alleles

Filtering AF 0.0236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0199%

Overall 0.00168% 27/1,610,124 alleles · ultra-rare exomes 15/1,458,198 · genomes 12/151,926 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0353%	2,829
Remaining individualsnot grpmax-eligible	0.00802%	12,464
European (non-Finnish)	8.48e-05%	1,178,570

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.Phe648=
Coding: c.1944T>C
MANE Select: NM_001367561
dbSNP: rs199869677
Type: single nucleotide variant
Location: chr1:62578894 (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 648: the c2 dock-type 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 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-phe648 (accessed [today's date]).

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