Is DOK7 p.Ala33Ser (c.97G>T) pathogenic?

DOK7 p.Ala33Ser (c.97G>T) is classified Uncertain significance in DOK7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-31). AlphaMissense: ambiguous (0.5361); Ultra-rare (popmax 0.0535%, amr); Associated with fetal akinesia deformation sequence 1.

What condition is associated with DOK7 p.Ala33Ser (c.97G>T)?

DOK7 p.Ala33Ser (c.97G>T) is associated with fetal akinesia deformation sequence 1, congenital myasthenic syndrome 10 (ClinVar).

How common is DOK7 p.Ala33Ser (c.97G>T) in the general population?

DOK7 p.Ala33Ser (c.97G>T) is ultra-rare (popmax 0.0535%, amr) (gnomAD).

What do computational predictors say about DOK7 p.Ala33Ser (c.97G>T)?

AlphaMissense predicts ambiguous (score 0.5361) — an in-silico prediction, not a clinical call.

DOK7 p.Ala33Ser

c.97G>T · rs1425852835 · VCV661865

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5361 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0535%, amr)

Conditions

fetal akinesia deformation sequence 1

Computational evidence

Protein change
AlphaMissense	0.5361	ambiguous
REVEL	0.483	indeterminate
SaProt	LLR -8.12	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 0.65, phastCons 1
Regional constraint	o/e 1.44	unconstrained · MANE · 30 kb · p 2.5e-31 · regional, not allelic
Overall
CADD	25.3	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 0.0535% Admixed American · 27/50,476 alleles

Filtering AF 0.0377% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0324%

Overall 0.00185% 28/1,513,268 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0535%	1,869
Remaining individualsnot grpmax-eligible	0.0017%	58,852

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.Ala33Ser
Coding: c.97G>T
MANE Select: NM_173660
dbSNP: rs1425852835
Type: single nucleotide variant
Location: chr4:3463548 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 33: the ph domain; a UniProt-annotated variant site (in cms10; results in reduced stimulation of musk autophosphorylation)

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.Ala33Thr Uncertain significance ★ ⚠ same residue
DOK7 p.Ala33Val Uncertain significance ★ ⚠ 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-ala33ser (accessed [today's date]).

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