Is DOK7 p.Arg402Gln (c.1205G>A) pathogenic?

DOK7 p.Arg402Gln (c.1205G>A) is classified Conflicting classifications of pathogenicity in DOK7 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.0835); Ultra-rare (popmax 0.0775%, afr); Associated with congenital myasthenic syndrome 10.

What condition is associated with DOK7 p.Arg402Gln (c.1205G>A)?

DOK7 p.Arg402Gln (c.1205G>A) is associated with congenital myasthenic syndrome 10, fetal akinesia deformation sequence 1 (ClinVar).

How common is DOK7 p.Arg402Gln (c.1205G>A) in the general population?

DOK7 p.Arg402Gln (c.1205G>A) is ultra-rare (popmax 0.0775%, afr) (gnomAD).

What do computational predictors say about DOK7 p.Arg402Gln (c.1205G>A)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

DOK7 p.Arg402Gln

c.1205G>A · rs370039804 · VCV575016

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0775%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital myasthenic syndrome 10

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -8.28	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 8	GERP 0.98, phastCons 1
Regional constraint	o/e 1.44	unconstrained · MANE · 30 kb · p 2.5e-31 · regional, not allelic
Overall
CADD	23.9	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 0.0775% African / African-American · 58/74,862 alleles

Filtering AF 0.0615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0557%

Overall 0.00708% 114/1,610,772 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0775%	1,291
Middle Eastern	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.00641%	15,590
South Asian	0.0055%	18,166
European (non-Finnish)	0.00373%	26,803
East Asian	0.00223%	44,778
Finnishnot grpmax-eligible	0.00161%	62,216

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.Arg402Gln
Coding: c.1205G>A
MANE Select: NM_173660
dbSNP: rs370039804
Type: single nucleotide variant
Location: chr4:3493191 (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

congenital myasthenic syndrome 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: fetal akinesia deformation sequence 1

Similar variants

DOK7 p.Arg402Trp Benign/Likely benign ★★ ⚠ 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-arg402gln (accessed [today's date]).

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