Is DOCK7 p.Arg1036Cys (c.3106C>T) pathogenic?

DOCK7 p.Arg1036Cys (c.3106C>T) is classified Uncertain significance in DOCK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely pathogenic (0.9017); Ultra-rare (popmax 0.0178%, eas); Associated with Inborn genetic diseases.

What condition is associated with DOCK7 p.Arg1036Cys (c.3106C>T)?

DOCK7 p.Arg1036Cys (c.3106C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK7 p.Arg1036Cys (c.3106C>T) in the general population?

DOCK7 p.Arg1036Cys (c.3106C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about DOCK7 p.Arg1036Cys (c.3106C>T)?

AlphaMissense predicts likely pathogenic (score 0.9017) — an in-silico prediction, not a clinical call.

DOCK7 p.Arg1036Cys

c.3106C>T · VCV4244017

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9017 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9017	likely pathogenic
REVEL	0.562	indeterminate
SaProt	LLR -15.64	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 175 kb · p 3.6e-10 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.0178% East Asian · 8/44,824 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000868% 14/1,613,322 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,603
African / African-American	0.00267%	37,436
South Asian	0.0022%	45,516
Remaining individualsnot grpmax-eligible	0.0016%	62,454
European (non-Finnish)	8.48e-05%	1,179,665

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: DOCK7
Protein: p.Arg1036Cys
Coding: c.3106C>T
MANE Select: NM_001367561
Type: single nucleotide variant
Location: chr1:62539832 (GRCh38)
Gene constraint: LOEUF 0.551 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 2 PDB

Full DOCK7 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

Similar variants

DOCK7 p.Arg1036His Uncertain significance ★★ ⚠ same residue
DOCK7 c.3781+4C>G Uncertain significance ★★ same condition
DOCK7 p.Ala1479Thr Uncertain significance ★★ ⚠ same condition
DOCK7 p.Ala205Thr Uncertain significance ★★ ⚠ same condition
DOCK7 p.Arg1266Gln Uncertain significance ★★ ⚠ same condition
DOCK7 p.Arg1358Gln Uncertain significance ★★ ⚠ same condition
DOCK7 p.Arg1380Gln Uncertain significance ★★ ⚠ same condition
DOCK7 p.Arg1634Gly Uncertain significance ★★ ⚠ 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/dock7-p-arg1036cys (accessed [today's date]).

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