Is DOK7 p.Leu65= (c.193C>T) pathogenic?

DOK7 p.Leu65= (c.193C>T) is classified Conflicting classifications of pathogenicity in DOK7 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-26). Ultra-rare (popmax 0.0312%, eas); Associated with congenital myasthenic syndrome 10.

What condition is associated with DOK7 p.Leu65= (c.193C>T)?

DOK7 p.Leu65= (c.193C>T) is associated with congenital myasthenic syndrome 10, fetal akinesia deformation sequence 1, fetal akinesia deformation sequence 3 (ClinVar).

How common is DOK7 p.Leu65= (c.193C>T) in the general population?

DOK7 p.Leu65= (c.193C>T) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

DOK7 p.Leu65=

c.193C>T · rs546630800 · VCV864125

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Conditions

congenital myasthenic syndrome 10

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.97, phastCons 1
Overall
CADD	11.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0312% East Asian · 14/44,878 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00106% 17/1,611,202 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,206
Remaining individualsnot grpmax-eligible	0.00321%	31,157
South Asian	0.0011%	90,992

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.Leu65=
Coding: c.193C>T
MANE Select: NM_173660
dbSNP: rs546630800
Type: single nucleotide variant
Location: chr4:3473498 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 65: the ph domain

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 fetal akinesia deformation sequence 3

Similar variants

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
DOK7 p.Cys412Ter Pathogenic ★★ same condition
DOK7 p.Gln151Ter 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-leu65 (accessed [today's date]).

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