Is DOK7 p.Arg402Pro (c.1205G>C) pathogenic?

DOK7 p.Arg402Pro (c.1205G>C) is classified Uncertain significance in DOK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-02). AlphaMissense: likely benign (0.1307); Very rare (popmax 0.00501%, amr); Associated with congenital myasthenic syndrome 10.

What condition is associated with DOK7 p.Arg402Pro (c.1205G>C)?

DOK7 p.Arg402Pro (c.1205G>C) is associated with congenital myasthenic syndrome 10, fetal akinesia deformation sequence 1 (ClinVar).

How common is DOK7 p.Arg402Pro (c.1205G>C) in the general population?

DOK7 p.Arg402Pro (c.1205G>C) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about DOK7 p.Arg402Pro (c.1205G>C)?

AlphaMissense predicts likely benign (score 0.1307) — an in-silico prediction, not a clinical call.

DOK7 p.Arg402Pro

c.1205G>C · rs370039804 · VCV1485408

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1307 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital myasthenic syndrome 10

Computational evidence

Protein change
AlphaMissense	0.1307	likely benign
REVEL	0.331	indeterminate
SaProt	LLR -9.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
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	23.5	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 0.00501% Admixed American · 3/59,876 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00155% 25/1,610,890 alleles · very rare exomes 23/1,458,582 · genomes 2/152,308 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,959
East Asian	0.00447%	22,383
European (non-Finnish)	0.00161%	62,069
Remaining individualsnot grpmax-eligible	0.0016%	62,382

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.Arg402Pro
Coding: c.1205G>C
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.Arg402Gln Conflicting classifications of pathogenicity ★ ⚠ 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-arg402pro (accessed [today's date]).

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