Is DOCK7 p.Pro2049Ser (c.6145C>T) pathogenic?

DOCK7 p.Pro2049Ser (c.6145C>T) is classified Uncertain significance in DOCK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-29). AlphaMissense: likely pathogenic (0.8802); Very rare (popmax 8.48e-05%, nfe); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Pro2049Ser (c.6145C>T)?

DOCK7 p.Pro2049Ser (c.6145C>T) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Pro2049Ser (c.6145C>T) in the general population?

DOCK7 p.Pro2049Ser (c.6145C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DOCK7 p.Pro2049Ser (c.6145C>T)?

AlphaMissense predicts likely pathogenic (score 0.8802) — an in-silico prediction, not a clinical call.

DOCK7 p.Pro2049Ser

c.6145C>T · rs2523703262 · VCV1968432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8802 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

developmental and epileptic encephalopathy, 23

Computational evidence

Protein change
AlphaMissense	0.8802	likely pathogenic
REVEL	0.327	indeterminate
SaProt	LLR -9.33	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 58 kb · p 5.9e-19 · regional, not allelic
Overall
CADD	24.8	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 8.48e-05% European (non-Finnish) · 1/1,179,890 alleles

Overall 0.000124% 2/1,613,912 alleles · very rare exomes 2/1,461,666 · genomes 0/152,246 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,016
European (non-Finnish)grpmax	8.48e-05%	1,179,889

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.Pro2049Ser
Coding: c.6145C>T
MANE Select: NM_001367561
dbSNP: rs2523703262
Type: single nucleotide variant
Location: chr1:62474049 (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 2049: the docker domain

Full DOCK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 23 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK7 p.Pro2049His Uncertain significance ★ ⚠ same residue
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

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-pro2049ser (accessed [today's date]).

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