Is DOCK7 p.Phe1885Val (c.5653T>G) pathogenic?

DOCK7 p.Phe1885Val (c.5653T>G) is classified Uncertain significance in DOCK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-11). AlphaMissense: likely pathogenic (0.8863); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DOCK7 p.Phe1885Val (c.5653T>G)?

DOCK7 p.Phe1885Val (c.5653T>G) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK7 p.Phe1885Val (c.5653T>G) in the general population?

DOCK7 p.Phe1885Val (c.5653T>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DOCK7 p.Phe1885Val (c.5653T>G)?

AlphaMissense predicts likely pathogenic (score 0.8863) — an in-silico prediction, not a clinical call.

DOCK7 p.Phe1885Val

c.5653T>G · rs777158952 · VCV2288513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8863 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8863	likely pathogenic
REVEL	0.728	pathogenic-leaning
SaProt	LLR -10.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 58 kb · p 5.9e-19 · regional, not allelic
Overall
CADD	26.9	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 8.48e-05% European (non-Finnish) · 1/1,179,518 alleles

Overall 0.00093% 15/1,612,762 alleles · very rare exomes 14/1,460,578 · genomes 1/152,184 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0219%	4,560
European (non-Finnish)grpmax	8.48e-05%	1,179,518

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe1885Val
Coding: c.5653T>G
MANE Select: NM_001367561
dbSNP: rs777158952
Type: single nucleotide variant
Location: chr1:62476138 (GRCh38)
Gene constraint: LOEUF 0.551 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 2 PDB
Residue 1885: the docker domain; an α-helix

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.Phe1885= Likely benign ★ 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-phe1885val (accessed [today's date]).

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