Is DOCK7 p.Ser999= (c.2997C>T) pathogenic?

DOCK7 p.Ser999= (c.2997C>T) is classified Likely benign in DOCK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-24). Ultra-rare (popmax 0.0178%, eas); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Ser999= (c.2997C>T)?

DOCK7 p.Ser999= (c.2997C>T) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Ser999= (c.2997C>T) in the general population?

DOCK7 p.Ser999= (c.2997C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

DOCK7 p.Ser999=

c.2997C>T · rs765019421 · VCV2891825

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

developmental and epileptic encephalopathy, 23

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.649	pathogenic-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.6	GERP -2.1
Overall
CADD	6.145	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,844 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00124% 20/1,612,562 alleles · ultra-rare exomes 17/1,460,486 · genomes 3/152,076 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,606
African / African-American	0.00935%	10,692
Remaining individualsnot grpmax-eligible	0.0032%	31,205
European (non-Finnish)	0.000254%	393,079

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.Ser999=
Coding: c.2997C>T
MANE Select: NM_001367561
dbSNP: rs765019421
Type: single nucleotide variant
Location: chr1:62542656 (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-ser999 (accessed [today's date]).

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