Is DOK7 p.Val32Met (c.94G>A) pathogenic?

DOK7 p.Val32Met (c.94G>A) is classified Conflicting classifications of pathogenicity in DOK7 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-05-12). AlphaMissense: likely pathogenic (0.9372); Very rare (popmax 0.0075%, eas); Associated with fetal akinesia deformation sequence 1.

What condition is associated with DOK7 p.Val32Met (c.94G>A)?

DOK7 p.Val32Met (c.94G>A) is associated with fetal akinesia deformation sequence 1, congenital myasthenic syndrome 10 (ClinVar).

How common is DOK7 p.Val32Met (c.94G>A) in the general population?

DOK7 p.Val32Met (c.94G>A) is very rare (popmax 0.0075%, eas) (gnomAD).

What do computational predictors say about DOK7 p.Val32Met (c.94G>A)?

AlphaMissense predicts likely pathogenic (score 0.9372) — an in-silico prediction, not a clinical call.

DOK7 p.Val32Met

c.94G>A · rs1417673287 · VCV948720

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9372 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0075%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

fetal akinesia deformation sequence 1

Computational evidence

Protein change
AlphaMissense	0.9372	likely pathogenic · top 8% in DOK7
REVEL	0.434	indeterminate
SaProt	LLR -9.06	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 0.65, phastCons 1
Regional constraint	o/e 1.44	unconstrained · MANE · 30 kb · p 2.5e-31 · regional, not allelic
Overall
CADD	25.3	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 0.0075% East Asian · 3/39,980 alleles

Filtering AF 0.00199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.000512% 7/1,366,042 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0075%	13,327
Admixed American	0.00595%	16,811
European (non-Finnish)	8.81e-05%	1,135,330

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.Val32Met
Coding: c.94G>A
MANE Select: NM_173660
dbSNP: rs1417673287
Type: single nucleotide variant
Location: chr4:3463545 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 32: the ph domain

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.Val32Leu Uncertain significance ★ ⚠ same residue
DOK7 p.Val32= Likely benign ★ 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-val32met (accessed [today's date]).

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