Is DOK7 p.Ala356= (c.1068G>A) pathogenic?

DOK7 p.Ala356= (c.1068G>A) is classified Likely benign in DOK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). Very rare (popmax 0.00924%, eas); Associated with fetal akinesia deformation sequence 1.

What condition is associated with DOK7 p.Ala356= (c.1068G>A)?

DOK7 p.Ala356= (c.1068G>A) is associated with fetal akinesia deformation sequence 1, congenital myasthenic syndrome 10 (ClinVar).

How common is DOK7 p.Ala356= (c.1068G>A) in the general population?

DOK7 p.Ala356= (c.1068G>A) is very rare (popmax 0.00924%, eas) (gnomAD).

DOK7 p.Ala356=

c.1068G>A · rs372407972 · VCV1922069

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00924%, eas)

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 -12	GERP -1.9
Overall
CADD	1.809	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00924% East Asian · 4/43,290 alleles

Filtering AF 0.00371% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00333%

Overall 0.00426% 67/1,574,598 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00924%	10,822
South Asian	0.00573%	17,460
European (non-Finnish)	0.00472%	21,181
African / African-American	0.00269%	37,194
Remaining individualsnot grpmax-eligible	0.00163%	61,216

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.Ala356=
Coding: c.1068G>A
MANE Select: NM_173660
dbSNP: rs372407972
Type: single nucleotide variant
Location: chr4:3493054 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61

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.Ala356Glu Uncertain significance ★★ ⚠ same residue
DOK7 p.Ala356Val Uncertain significance ★★ ⚠ same residue
DOK7 p.Ala356Pro Uncertain significance ★ ⚠ same residue
DOK7 p.Ala356Thr 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

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-ala356 (accessed [today's date]).

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