Is DOK7 p.Arg402Trp (c.1204C>T) pathogenic?

DOK7 p.Arg402Trp (c.1204C>T) is classified Benign/Likely benign in DOK7 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.1045); Low-frequency (popmax 1.63%, afr); Associated with fetal akinesia deformation sequence 1.

What condition is associated with DOK7 p.Arg402Trp (c.1204C>T)?

DOK7 p.Arg402Trp (c.1204C>T) is associated with fetal akinesia deformation sequence 1, congenital myasthenic syndrome 10 (ClinVar).

How common is DOK7 p.Arg402Trp (c.1204C>T) in the general population?

DOK7 p.Arg402Trp (c.1204C>T) is low-frequency (popmax 1.63%, afr) (gnomAD).

What do computational predictors say about DOK7 p.Arg402Trp (c.1204C>T)?

AlphaMissense predicts likely benign (score 0.1045) — an in-silico prediction, not a clinical call.

DOK7 p.Arg402Trp

c.1204C>T · rs149905649 · VCV262867

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1045 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.63%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

fetal akinesia deformation sequence 1

Computational evidence

Protein change
AlphaMissense	0.1045	likely benign
REVEL	0.316	indeterminate
SaProt	LLR -10.13	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -0.12, phastCons 0.013
Regional constraint	o/e 1.44	unconstrained · MANE · 30 kb · p 2.5e-31 · regional, not allelic
Overall
CADD	20.6	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 1.63% African / African-American · 1,220/74,980 alleles

Filtering AF 1.55% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.52%

Overall 0.146% 2,356/1,610,674 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.63%	61
Admixed American	0.257%	389
Remaining individualsnot grpmax-eligible	0.109%	917
European (non-Finnish)	0.0764%	1,309
Middle Eastern	0.066%	1,516
Finnishnot grpmax-eligible	0.0113%	8,879
South Asian	0.0022%	45,386

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: DOK7
Protein: p.Arg402Trp
Coding: c.1204C>T
MANE Select: NM_173660
dbSNP: rs149905649
Type: single nucleotide variant
Location: chr4:3493190 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 402: a UniProt-annotated variant site (in)

Full DOK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

fetal akinesia deformation sequence 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 10

Similar variants

DOK7 p.Arg402Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
DOK7 p.Arg402Pro Uncertain significance ★ ⚠ same residue
DOK7 p.Arg402= Likely benign ★ same residue
DOK7 c.331+1G>T Pathogenic ★★ same condition
DOK7 c.332-1G>A Likely pathogenic ★★ same condition
DOK7 c.332-1G>C Likely pathogenic ★★ same condition
DOK7 c.332-1G>T Likely pathogenic ★★ same condition
DOK7 p.Arg158Gln 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/dok7-p-arg402trp (accessed [today's date]).

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