Is DOCK7 p.Ser943Phe (c.2828C>T) pathogenic?

DOCK7 p.Ser943Phe (c.2828C>T) is classified Likely benign in DOCK7 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1566); Rare (popmax 0.316%, afr); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Ser943Phe (c.2828C>T)?

DOCK7 p.Ser943Phe (c.2828C>T) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Ser943Phe (c.2828C>T) in the general population?

DOCK7 p.Ser943Phe (c.2828C>T) is rare (popmax 0.316%, afr) (gnomAD).

What do computational predictors say about DOCK7 p.Ser943Phe (c.2828C>T)?

AlphaMissense predicts likely benign (score 0.1566) — an in-silico prediction, not a clinical call.

DOCK7 p.Ser943Phe

c.2828C>T · rs61742951 · VCV475135

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1566 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.316%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 23

Computational evidence

Protein change
AlphaMissense	0.1566	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -8.22	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 9.9	GERP 2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 175 kb · p 3.6e-10 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.316% African / African-American · 231/73,100 alleles

Filtering AF 0.283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.27%

Overall 0.0185% 287/1,549,740 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.316%	316
Admixed American	0.0785%	1,274
Remaining individualsnot grpmax-eligible	0.0216%	4,620
Middle Eastern	0.0167%	5,984
South Asian	0.00119%	84,018
European (non-Finnish)	8.72e-05%	1,146,450

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.Ser943Phe
Coding: c.2828C>T
MANE Select: NM_001367561
dbSNP: rs61742951
Type: single nucleotide variant
Location: chr1:62544978 (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 943: 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.Ser943Pro Uncertain significance ★ ⚠ same residue
DOCK7 p.Ser943Tyr Uncertain significance ★ ⚠ same residue
DOCK7 p.Ser943= Likely benign ★ 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-ser943phe (accessed [today's date]).

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