Is DOK7 p.Arg323Cys (c.967C>T) pathogenic?

DOK7 p.Arg323Cys (c.967C>T) is classified Benign in DOK7 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0717); Low-frequency (popmax 2.78%, afr); Associated with fetal akinesia deformation sequence 1.

What condition is associated with DOK7 p.Arg323Cys (c.967C>T)?

DOK7 p.Arg323Cys (c.967C>T) is associated with fetal akinesia deformation sequence 1, congenital myasthenic syndrome 10 (ClinVar).

How common is DOK7 p.Arg323Cys (c.967C>T) in the general population?

DOK7 p.Arg323Cys (c.967C>T) is low-frequency (popmax 2.78%, afr) (gnomAD).

What do computational predictors say about DOK7 p.Arg323Cys (c.967C>T)?

AlphaMissense predicts likely benign (score 0.0717) — an in-silico prediction, not a clinical call.

DOK7 p.Arg323Cys

c.967C>T · rs150728781 · VCV128917

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0717 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.78%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

fetal akinesia deformation sequence 1

Computational evidence

Protein change
AlphaMissense	0.0717	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -11.11	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -0.008, phastCons 0.99
Regional constraint	o/e 1.44	unconstrained · MANE · 30 kb · p 2.5e-31 · regional, not allelic
Overall
CADD	18.35	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 2.78% African / African-American · 2,049/73,702 alleles

Filtering AF 2.68% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.64%

Overall 0.149% 2,315/1,553,432 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.78%	36
Remaining individualsnot grpmax-eligible	0.201%	499
Admixed American	0.144%	694
Middle Eastern	0.05%	2,001
South Asian	0.00703%	14,224
European (non-Finnish)	0.00503%	19,864
Finnishnot grpmax-eligible	0.00379%	26,362
East Asian	0.00241%	41,566

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.Arg323Cys
Coding: c.967C>T
MANE Select: NM_173660
dbSNP: rs150728781
Type: single nucleotide variant
Location: chr4:3492953 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 323: a UniProt-annotated variant site (in); 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.Arg323His 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
DOK7 p.Cys412Ter 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-arg323cys (accessed [today's date]).

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