Is DOK7 p.Thr438Arg (c.1313C>G) pathogenic?

DOK7 p.Thr438Arg (c.1313C>G) is classified Conflicting classifications of pathogenicity in DOK7 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0888); Rare (popmax 0.271%, eas); Associated with fetal akinesia deformation sequence 1.

What condition is associated with DOK7 p.Thr438Arg (c.1313C>G)?

DOK7 p.Thr438Arg (c.1313C>G) is associated with fetal akinesia deformation sequence 1, congenital myasthenic syndrome 10 (ClinVar).

How common is DOK7 p.Thr438Arg (c.1313C>G) in the general population?

DOK7 p.Thr438Arg (c.1313C>G) is rare (popmax 0.271%, eas) (gnomAD).

What do computational predictors say about DOK7 p.Thr438Arg (c.1313C>G)?

AlphaMissense predicts likely benign (score 0.0888) — an in-silico prediction, not a clinical call.

DOK7 p.Thr438Arg

c.1313C>G · rs376805794 · VCV198625

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0888 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.271%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

fetal akinesia deformation sequence 1

Computational evidence

Protein change
AlphaMissense	0.0888	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -5.52	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 -4.2	GERP -1.8
Regional constraint	o/e 1.44	unconstrained · MANE · 30 kb · p 2.5e-31 · regional, not allelic
Overall
CADD	0.259	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 0.271% East Asian · 121/44,614 alleles

Filtering AF 0.232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.217%

Overall 0.00971% 156/1,607,038 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.271%	369
Remaining individualsnot grpmax-eligible	0.0483%	2,072
Admixed American	0.00336%	29,720
South Asian	0.00111%	90,420
European (non-Finnish)	0.00017%	588,658

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.Thr438Arg
Coding: c.1313C>G
MANE Select: NM_173660
dbSNP: rs376805794
Type: single nucleotide variant
Location: chr4:3493299 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 438: the 'disordered' region

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.Thr438Met Uncertain significance ★★ ⚠ same residue
DOK7 p.Thr438= Likely benign ★ same residue
DOK7 p.Thr438fs Pathogenic ★ 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-thr438arg (accessed [today's date]).

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