Is DOCK10 p.Asn1933Lys (c.5799C>A) pathogenic?

DOCK10 p.Asn1933Lys (c.5799C>A) is classified Uncertain significance in DOCK10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely pathogenic (0.8056); Ultra-rare (popmax 0.0174%, afr).

How common is DOCK10 p.Asn1933Lys (c.5799C>A) in the general population?

DOCK10 p.Asn1933Lys (c.5799C>A) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about DOCK10 p.Asn1933Lys (c.5799C>A)?

AlphaMissense predicts likely pathogenic (score 0.8056) — an in-silico prediction, not a clinical call.

DOCK10 p.Asn1933Lys

c.5799C>A · VCV4661659

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8056 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8056	likely pathogenic
REVEL	0.087	moderately benign-leaning
SaProt	LLR -12.15	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 58 kb · p 1e-10 · regional, not allelic
Overall
CADD	21.3	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 0.0174% African / African-American · 13/74,902 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.000868% 14/1,612,908 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,762
European (non-Finnish)	8.48e-05%	1,179,404

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: DOCK10
Protein: p.Asn1933Lys
Coding: c.5799C>A
MANE Select: NM_014689
Type: single nucleotide variant
Location: chr2:224778141 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.47 · 4 PDB
Residue 1933: the docker domain

Full DOCK10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK10 p.Asp2034= Benign ★★ same type
DOCK10 p.Ser1349= Benign ★★ same type
DOCK10 p.Thr1950= Benign ★★ same type
DOCK10 p.Ala112Ser Uncertain significance ★ ⚠ same type
DOCK10 p.Ala1135Thr Uncertain significance ★ ⚠ same type
DOCK10 p.Ala1175Thr Uncertain significance ★ ⚠ same type
DOCK10 p.Ala1177Ser Uncertain significance ★ ⚠ same type
DOCK10 p.Ala1271Glu Uncertain significance ★ ⚠ 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/dock10-p-asn1933lys (accessed [today's date]).

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