Is DOCK11 p.Glu482Val (c.1445A>T) pathogenic?

DOCK11 p.Glu482Val (c.1445A>T) is classified Uncertain significance in DOCK11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). AlphaMissense: likely pathogenic (0.9095); Very rare (popmax 0.00438%, amr).

How common is DOCK11 p.Glu482Val (c.1445A>T) in the general population?

DOCK11 p.Glu482Val (c.1445A>T) is very rare (popmax 0.00438%, amr) (gnomAD).

What do computational predictors say about DOCK11 p.Glu482Val (c.1445A>T)?

AlphaMissense predicts likely pathogenic (score 0.9095) — an in-silico prediction, not a clinical call.

DOCK11 p.Glu482Val

c.1445A>T · VCV3504385

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9095 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00438%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9095	likely pathogenic
REVEL	0.535	indeterminate
SaProt	LLR -13.90	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 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 190 kb · p 2e-21 · regional, not allelic
Overall
CADD	22.0	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 0.00438% Admixed American · 2/45,649 alleles

Filtering AF 0.000726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000272%

Overall 0.000664% 8/1,205,167 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00438%	22,824
Remaining individualsnot grpmax-eligible	0.00422%	23,683
African / African-American	0.00175%	57,113
European (non-Finnish)	0.000337%	297,108

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: DOCK11
Protein: p.Glu482Val
Coding: c.1445A>T
MANE Select: NM_144658
Type: single nucleotide variant
Location: chrX:118578580 (GRCh38)
Structure: AlphaFold pLDDT 79.65

Full DOCK11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK11 p.Ala1222Val Uncertain significance ★★ ⚠ same type
DOCK11 p.Ala1665Val Uncertain significance ★★ ⚠ same type
DOCK11 p.Leu781His Uncertain significance ★★ ⚠ same type
DOCK11 p.Gln866Arg Benign ★★ same type
DOCK11 p.Ser842Leu Likely benign ★★ same type
DOCK11 c.1718+5G>A Pathogenic ★ same type
DOCK11 c.392+1G>A Likely pathogenic ★ same type
DOCK11 c.4582-1G>A Likely pathogenic ★ same type

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/dock11-p-glu482val (accessed [today's date]).

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