Is DOK7 p.Pro324= (c.972G>A) pathogenic?

DOK7 p.Pro324= (c.972G>A) is classified Likely benign in DOK7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Rare (popmax 0.118%, afr); Associated with congenital myasthenic syndrome 10.

What condition is associated with DOK7 p.Pro324= (c.972G>A)?

DOK7 p.Pro324= (c.972G>A) is associated with congenital myasthenic syndrome 10, fetal akinesia deformation sequence 1 (ClinVar).

How common is DOK7 p.Pro324= (c.972G>A) in the general population?

DOK7 p.Pro324= (c.972G>A) is rare (popmax 0.118%, afr) (gnomAD).

DOK7 p.Pro324=

c.972G>A · rs373041663 · VCV511325

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.118%, afr)

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 -20	GERP -2.2
Overall
CADD	0.013	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.118% African / African-American · 87/73,722 alleles

Filtering AF 0.098% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0905%

Overall 0.0102% 158/1,552,650 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.118%	847
South Asian	0.0352%	2,842
East Asian	0.0337%	2,968
Admixed American	0.00962%	10,392
Remaining individualsnot grpmax-eligible	0.00663%	15,086
European (non-Finnish)	0.00156%	63,992

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.Pro324=
Coding: c.972G>A
MANE Select: NM_173660
dbSNP: rs373041663
Type: single nucleotide variant
Location: chr4:3492958 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 324: the 'disordered' region

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.Pro324Leu Uncertain significance ★★ ⚠ same residue
DOK7 p.Pro324Arg 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-pro324 (accessed [today's date]).

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