Is DOCK7 p.Asn1981Ser (c.5942A>G) pathogenic?

DOCK7 p.Asn1981Ser (c.5942A>G) is classified Uncertain significance in DOCK7 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-15). AlphaMissense: likely benign (0.0843); Very rare (popmax 0.00509%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DOCK7 p.Asn1981Ser (c.5942A>G)?

DOCK7 p.Asn1981Ser (c.5942A>G) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Asn1981Ser (c.5942A>G) in the general population?

DOCK7 p.Asn1981Ser (c.5942A>G) is very rare (popmax 0.00509%, nfe) (gnomAD).

What do computational predictors say about DOCK7 p.Asn1981Ser (c.5942A>G)?

AlphaMissense predicts likely benign (score 0.0843) — an in-silico prediction, not a clinical call.

DOCK7 p.Asn1981Ser

c.5942A>G · rs145796299 · VCV2155426

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0843 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00509%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0843	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -5.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 1.5, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 58 kb · p 5.9e-19 · regional, not allelic
Overall
CADD	23.7	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00509% European (non-Finnish) · 60/1,179,892 alleles

Filtering AF 0.00402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00362%

Overall 0.00415% 67/1,613,824 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00509%	19,665
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
South Asian	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0016%	62,480
Finnishnot grpmax-eligible	0.00156%	63,968
African / African-American	0.00133%	74,930

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.Asn1981Ser
Coding: c.5942A>G
MANE Select: NM_001367561
dbSNP: rs145796299
Type: single nucleotide variant
Location: chr1:62475726 (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 1981: the docker domain; a β-strand

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

Also linked: developmental and epileptic encephalopathy, 23

Similar variants

DOCK7 c.4924-1G>A Pathogenic/Likely pathogenic ★★ same condition
DOCK7 p.Arg1380Ter Pathogenic ★★ same condition
DOCK7 p.Arg1415Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK7 p.Arg429Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK7 p.Arg445Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK7 c.3781+4C>G Uncertain significance ★★ same condition
DOCK7 c.38+6T>C Uncertain significance ★★ same condition
DOCK7 p.Ala1479Thr 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-asn1981ser (accessed [today's date]).

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