Is DOK7 p.Leu385Pro (c.1154T>C) pathogenic?

DOK7 p.Leu385Pro (c.1154T>C) is classified Uncertain significance in DOK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.0731); Absent from gnomAD v4.1; Associated with fetal akinesia deformation sequence 1.

What condition is associated with DOK7 p.Leu385Pro (c.1154T>C)?

DOK7 p.Leu385Pro (c.1154T>C) is associated with fetal akinesia deformation sequence 1, congenital myasthenic syndrome 10 (ClinVar).

How common is DOK7 p.Leu385Pro (c.1154T>C) in the general population?

DOK7 p.Leu385Pro (c.1154T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOK7 p.Leu385Pro (c.1154T>C)?

AlphaMissense predicts likely benign (score 0.0731) — an in-silico prediction, not a clinical call.

DOK7 p.Leu385Pro

c.1154T>C · rs1728632885 · VCV1020442

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0731 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,601,382)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

fetal akinesia deformation sequence 1

Computational evidence

Protein change
AlphaMissense	0.0731	likely benign
REVEL	0.382	indeterminate
SaProt	LLR -5.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.71	GERP 0.98, phastCons 0.82
Regional constraint	o/e 1.44	unconstrained · MANE · 30 kb · p 2.5e-31 · regional, not allelic
Overall
CADD	19.03	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,601,382). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DOK7
Protein: p.Leu385Pro
Coding: c.1154T>C
MANE Select: NM_173660
dbSNP: rs1728632885
Type: single nucleotide variant
Location: chr4:3493140 (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.Leu385= Likely benign ★ same residue
DOK7 p.Leu385fs Pathogenic ★ 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-leu385pro (accessed [today's date]).

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