Is DOK7 p.Lys207= (c.621G>A) pathogenic?

DOK7 p.Lys207= (c.621G>A) is classified Likely benign in DOK7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-15). Very rare (popmax 0.00169%, amr); Associated with Inborn genetic diseases.

What condition is associated with DOK7 p.Lys207= (c.621G>A)?

DOK7 p.Lys207= (c.621G>A) is associated with Inborn genetic diseases, congenital myasthenic syndrome 10, fetal akinesia deformation sequence 1 (ClinVar).

How common is DOK7 p.Lys207= (c.621G>A) in the general population?

DOK7 p.Lys207= (c.621G>A) is very rare (popmax 0.00169%, amr) (gnomAD).

DOK7 p.Lys207=

c.621G>A · rs760545801 · VCV2923721

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00169%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.336	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 1.2, phastCons 1
Overall
CADD	10.76	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% Admixed American · 1/59,312 alleles

Overall 0.000138% 2/1,451,326 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00169%	59,312
Remaining individualsnot grpmax-eligible	0.00161%	62,012

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.Lys207=
Coding: c.621G>A
MANE Select: NM_173660
dbSNP: rs760545801
Type: single nucleotide variant
Location: chr4:3485627 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 207: the irs-type ptb domain

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.Lys207Gln 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-lys207 (accessed [today's date]).

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