Is DOK7 p.Ser354Phe (c.1061C>T) pathogenic?

DOK7 p.Ser354Phe (c.1061C>T) is classified Pathogenic in DOK7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-03-01). AlphaMissense: ambiguous (0.3633); Very rare (popmax 0.00693%, eas); Associated with congenital myasthenic syndrome 10.

What condition is associated with DOK7 p.Ser354Phe (c.1061C>T)?

DOK7 p.Ser354Phe (c.1061C>T) is associated with congenital myasthenic syndrome 10 (ClinVar).

How common is DOK7 p.Ser354Phe (c.1061C>T) in the general population?

DOK7 p.Ser354Phe (c.1061C>T) is very rare (popmax 0.00693%, eas) (gnomAD).

What do computational predictors say about DOK7 p.Ser354Phe (c.1061C>T)?

AlphaMissense predicts ambiguous (score 0.3633) — an in-silico prediction, not a clinical call.

DOK7 p.Ser354Phe

c.1061C>T · rs756015202 · VCV544830

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3633 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00693%, eas)

Conditions

congenital myasthenic syndrome 10

Computational evidence

Protein change
AlphaMissense	0.3633	ambiguous
REVEL	0.344	indeterminate
SaProt	LLR -10.63	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP -0.13, phastCons 1
Regional constraint	o/e 1.44	unconstrained · MANE · 30 kb · p 2.5e-31 · regional, not allelic
Overall
CADD	26.0	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 0.00693% East Asian · 3/43,304 alleles

Filtering AF 0.00297% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.000844% 12/1,421,150 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00693%	14,435
South Asian	0.00688%	14,532
Remaining individualsnot grpmax-eligible	0.00163%	61,230
European (non-Finnish)	0.000172%	582,201

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.Ser354Phe
Coding: c.1061C>T
MANE Select: NM_173660
dbSNP: rs756015202
Type: single nucleotide variant
Location: chr4:3493047 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61

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

Similar variants

DOK7 p.Ser354= Likely benign ★ same residue
DOK7 p.Ser354fs 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
DOK7 p.Arg201Ter 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-ser354phe (accessed [today's date]).

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