Is DOCK7 p.Ile919= (c.2757C>T) pathogenic?

DOCK7 p.Ile919= (c.2757C>T) is classified Likely benign in DOCK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-09). Very rare (popmax 0.00838%, amr); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Ile919= (c.2757C>T)?

DOCK7 p.Ile919= (c.2757C>T) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Ile919= (c.2757C>T) in the general population?

DOCK7 p.Ile919= (c.2757C>T) is very rare (popmax 0.00838%, amr) (gnomAD).

DOCK7 p.Ile919=

c.2757C>T · rs752071248 · VCV541930

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00838%, amr)

Conditions

developmental and epileptic encephalopathy, 23

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.399	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.7	GERP -4
Overall
CADD	6.543	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00838% Admixed American · 5/59,638 alleles

Filtering AF 0.00325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00208%

Overall 0.00155% 25/1,609,860 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00838%	11,928
Remaining individualsnot grpmax-eligible	0.00481%	20,771
African / African-American	0.00268%	37,338
South Asian	0.00221%	45,182
Finnishnot grpmax-eligible	0.00156%	63,914
European (non-Finnish)	0.00102%	98,145

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.Ile919=
Coding: c.2757C>T
MANE Select: NM_001367561
dbSNP: rs752071248
Type: single nucleotide variant
Location: chr1:62552741 (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 919: the 'disordered' region

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.Ile919Thr Uncertain significance ★ same residue
DOCK7 p.Ile919Phe Uncertain significance ★★ same residue
DOCK7 p.Ile919Val 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

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-ile919 (accessed [today's date]).

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