Is DOK7 p.Arg105His (c.314G>A) pathogenic?

DOK7 p.Arg105His (c.314G>A) is classified Uncertain significance in DOK7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-25). AlphaMissense: likely benign (0.1657); Ultra-rare (popmax 0.0226%, mid); Associated with Inborn genetic diseases.

What condition is associated with DOK7 p.Arg105His (c.314G>A)?

DOK7 p.Arg105His (c.314G>A) is associated with Inborn genetic diseases, congenital myasthenic syndrome 10, fetal akinesia deformation sequence 1 (ClinVar).

How common is DOK7 p.Arg105His (c.314G>A) in the general population?

DOK7 p.Arg105His (c.314G>A) is ultra-rare (popmax 0.0226%, mid) (gnomAD).

What do computational predictors say about DOK7 p.Arg105His (c.314G>A)?

AlphaMissense predicts likely benign (score 0.1657) — an in-silico prediction, not a clinical call.

DOK7 p.Arg105His

c.314G>A · rs776352781 · VCV1503294

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1657 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0226%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1657	likely benign
REVEL	0.641	indeterminate
SaProt	LLR -12.07	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.97, phastCons 1
Regional constraint	o/e 1.44	unconstrained · MANE · 30 kb · p 2.5e-31 · regional, not allelic
Overall
CADD	29.8	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 0.0226% Middle Eastern · 1/4,424 alleles

Filtering AF 0.00819% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00604%

Overall 0.00139% 22/1,584,156 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0226%	4,424
Admixed American	0.0158%	6,344
African / African-American	0.00673%	14,853
South Asian	0.00336%	29,755
East Asian	0.0023%	43,524
Remaining individualsnot grpmax-eligible	0.00164%	61,030
European (non-Finnish)	0.000172%	581,135

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.Arg105His
Coding: c.314G>A
MANE Select: NM_173660
dbSNP: rs776352781
Type: single nucleotide variant
Location: chr4:3473619 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 105: the ph domain; 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.Arg105Cys Conflicting classifications of pathogenicity ★ ⚠ 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-arg105his (accessed [today's date]).

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