Is DOK7 p.Ser256= (c.768T>C) pathogenic?

DOK7 p.Ser256= (c.768T>C) is classified Likely benign in DOK7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-29). Very rare (popmax 0.00233%, sas); Associated with Inborn genetic diseases.

What condition is associated with DOK7 p.Ser256= (c.768T>C)?

DOK7 p.Ser256= (c.768T>C) is associated with Inborn genetic diseases, congenital myasthenic syndrome 10, fetal akinesia deformation sequence 1 (ClinVar).

How common is DOK7 p.Ser256= (c.768T>C) in the general population?

DOK7 p.Ser256= (c.768T>C) is very rare (popmax 0.00233%, sas) (gnomAD).

DOK7 p.Ser256=

c.768T>C · rs755782908 · VCV2924805

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00233%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.498	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6.9	GERP -2
Overall
CADD	0.785	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00233% South Asian · 2/85,774 alleles

Filtering AF 0.00097% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000801%

Overall 0.00127% 20/1,573,666 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00233%	42,887
European (non-Finnish)	0.00155%	64,408

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.Ser256=
Coding: c.768T>C
MANE Select: NM_173660
dbSNP: rs755782908
Type: single nucleotide variant
Location: chr4:3489792 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 256: the 'disordered' region

Full DOK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 10 fetal akinesia deformation sequence 1

Similar variants

DOK7 p.Ser256Gly Uncertain significance ★★ ⚠ same residue
DOK7 p.Ser256Arg 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-ser256 (accessed [today's date]).

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