Is DOCK1 p.Asn1809Lys (c.5427C>A) pathogenic?

DOCK1 p.Asn1809Lys (c.5427C>A) is classified Uncertain significance in DOCK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-10). AlphaMissense: likely benign (0.3242); Very rare (popmax 0.000254%, nfe).

How common is DOCK1 p.Asn1809Lys (c.5427C>A) in the general population?

DOCK1 p.Asn1809Lys (c.5427C>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about DOCK1 p.Asn1809Lys (c.5427C>A)?

AlphaMissense predicts likely benign (score 0.3242) — an in-silico prediction, not a clinical call.

DOCK1 p.Asn1809Lys

c.5427C>A · VCV4661635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3242 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3242	likely benign
REVEL	0.314	indeterminate
SaProt	LLR -7.49	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -3.3
Regional constraint	o/e 0.91	unconstrained · MANE · 32 kb · p 0.07 · regional, not allelic
Overall
CADD	1.919	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM N1788K vs ClinVar N1809K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,304 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,460,328 alleles · very rare

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: DOCK1
Protein: p.Asn1809Lys
Coding: c.5427C>A
MANE Select: NM_001290223
Type: single nucleotide variant
Location: chr10:127447407 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.63 · 1 PDB
Residue 1809: the 'disordered' region; the 'interaction with nck2 second and third sh3 domain (minor)' region

Full DOCK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK1 p.Asn1809= Likely benign ★ same residue
DOCK1 p.Pro1783Ser Uncertain significance ★★ ⚠ same type
DOCK1 p.Ala1185Thr Uncertain significance ★ ⚠ same type
DOCK1 p.Ala151Thr Uncertain significance ★ ⚠ same type
DOCK1 p.Ala1578Ser Uncertain significance ★ ⚠ same type
DOCK1 p.Ala1590Gly Uncertain significance ★ ⚠ same type
DOCK1 p.Ala1620Val Uncertain significance ★ ⚠ same type
DOCK1 p.Ala1689Ser 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/dock1-p-asn1809lys (accessed [today's date]).

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