Is DOK7 p.Ser439= (c.1317C>T) pathogenic?

DOK7 p.Ser439= (c.1317C>T) is classified Benign in DOK7 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Low-frequency (popmax 4.73%, afr); Associated with fetal akinesia deformation sequence 1.

What condition is associated with DOK7 p.Ser439= (c.1317C>T)?

DOK7 p.Ser439= (c.1317C>T) is associated with fetal akinesia deformation sequence 1, congenital myasthenic syndrome 10 (ClinVar).

How common is DOK7 p.Ser439= (c.1317C>T) in the general population?

DOK7 p.Ser439= (c.1317C>T) is low-frequency (popmax 4.73%, afr) (gnomAD).

DOK7 p.Ser439=

c.1317C>T · rs16844467 · VCV128909

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.73%, afr)

Conditions

fetal akinesia deformation sequence 1

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 -3.6	GERP -1.9
Overall
CADD	1.384	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.73% African / African-American · 3,540/74,898 alleles

Filtering AF 4.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.54%

Overall 0.277% 4,447/1,606,308 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.73%	21
Middle Eastern	0.397%	252
Admixed American	0.357%	280
Remaining individualsnot grpmax-eligible	0.272%	368
European (non-Finnish)	0.0393%	2,547
East Asian	0.0314%	3,185
South Asian	0.0244%	4,106
Ashkenazi Jewishnot grpmax-eligible	0.00681%	14,681
Finnishnot grpmax-eligible	0.00324%	30,895

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.Ser439=
Coding: c.1317C>T
MANE Select: NM_173660
dbSNP: rs16844467
Type: single nucleotide variant
Location: chr4:3493303 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 439: 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 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-ser439 (accessed [today's date]).

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