Is DOCK7 p.Ser1499= (c.4497C>G) pathogenic?

DOCK7 p.Ser1499= (c.4497C>G) is classified Likely benign in DOCK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-24). Very rare (popmax 0.00382%, nfe); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Ser1499= (c.4497C>G)?

DOCK7 p.Ser1499= (c.4497C>G) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Ser1499= (c.4497C>G) in the general population?

DOCK7 p.Ser1499= (c.4497C>G) is very rare (popmax 0.00382%, nfe) (gnomAD).

DOCK7 p.Ser1499=

c.4497C>G · rs145123324 · VCV475149

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00382%, nfe)

Conditions

developmental and epileptic encephalopathy, 23

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.077	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Overall
CADD	10.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00382% European (non-Finnish) · 45/1,178,664 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00292% 47/1,610,214 alleles · very rare exomes 45/1,458,324 · genomes 2/151,890 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00382%	26,193
Remaining individualsnot grpmax-eligible	0.0016%	62,308
African / African-American	0.00134%	74,566

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.Ser1499=
Coding: c.4497C>G
MANE Select: NM_001367561
dbSNP: rs145123324
Type: single nucleotide variant
Location: chr1:62505796 (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-ser1499 (accessed [today's date]).

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