Is DOK7 p.Ala99Val (c.296C>T) pathogenic?

DOK7 p.Ala99Val (c.296C>T) is classified Conflicting classifications of pathogenicity in DOK7 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.1071); Rare (popmax 0.14%, afr); Associated with congenital myasthenic syndrome 10.

What condition is associated with DOK7 p.Ala99Val (c.296C>T)?

DOK7 p.Ala99Val (c.296C>T) is associated with congenital myasthenic syndrome 10, fetal akinesia deformation sequence 1 (ClinVar).

How common is DOK7 p.Ala99Val (c.296C>T) in the general population?

DOK7 p.Ala99Val (c.296C>T) is rare (popmax 0.14%, afr) (gnomAD).

What do computational predictors say about DOK7 p.Ala99Val (c.296C>T)?

AlphaMissense predicts likely benign (score 0.1071) — an in-silico prediction, not a clinical call.

DOK7 p.Ala99Val

c.296C>T · rs138010842 · VCV262871

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1071 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.14%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital myasthenic syndrome 10

Computational evidence

Protein change
AlphaMissense	0.1071	likely benign
REVEL	0.593	indeterminate
SaProt	LLR -6.37	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.5	GERP 0.97, phastCons 1
Regional constraint	o/e 1.44	unconstrained · MANE · 30 kb · p 2.5e-31 · regional, not allelic
Overall
CADD	25.7	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 0.14% African / African-American · 105/74,760 alleles

Filtering AF 0.119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.111%

Overall 0.0146% 234/1,601,886 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.14%	712
Admixed American	0.022%	4,546
Remaining individualsnot grpmax-eligible	0.0146%	6,861
European (non-Finnish)	0.00861%	11,621
South Asian	0.00442%	22,615
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,436
Finnishnot grpmax-eligible	0.00159%	62,892

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.Ala99Val
Coding: c.296C>T
MANE Select: NM_173660
dbSNP: rs138010842
Type: single nucleotide variant
Location: chr4:3473601 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 99: the ph domain; a UniProt-annotated variant site (in)

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

Disease context

congenital myasthenic syndrome 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: fetal akinesia deformation sequence 1

Similar variants

DOK7 p.Ala99= 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
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-ala99val (accessed [today's date]).

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