Is DOCK7 p.Arg1618His (c.4853G>A) pathogenic?

DOCK7 p.Arg1618His (c.4853G>A) is classified Uncertain significance in DOCK7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-20). AlphaMissense: likely benign (0.1421); Very rare (popmax 0.00267%, afr); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Arg1618His (c.4853G>A)?

DOCK7 p.Arg1618His (c.4853G>A) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Arg1618His (c.4853G>A) in the general population?

DOCK7 p.Arg1618His (c.4853G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DOCK7 p.Arg1618His (c.4853G>A)?

AlphaMissense predicts likely benign (score 0.1421) — an in-silico prediction, not a clinical call.

DOCK7 p.Arg1618His

c.4853G>A · rs142960242 · VCV565548

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1421 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 23

Computational evidence

Protein change
AlphaMissense	0.1421	likely benign
REVEL	0.283	benign-leaning
SaProt	LLR -6.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 58 kb · p 5.9e-19 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,850 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,613,276 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,425
European (non-Finnish)	0.000678%	147,446

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.Arg1618His
Coding: c.4853G>A
MANE Select: NM_001367561
dbSNP: rs142960242
Type: single nucleotide variant
Location: chr1:62496409 (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 p.Arg1618Cys 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
DOCK7 c.3781+4C>G Uncertain significance ★★ same condition
DOCK7 c.38+6T>C 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-arg1618his (accessed [today's date]).

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