Is DOCK7 p.Ser1573Gly (c.4717A>G) pathogenic?

DOCK7 p.Ser1573Gly (c.4717A>G) is classified Conflicting classifications of pathogenicity in DOCK7 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-04-01). AlphaMissense: ambiguous (0.4149); Ultra-rare (popmax 0.0822%, mid); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Ser1573Gly (c.4717A>G)?

DOCK7 p.Ser1573Gly (c.4717A>G) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Ser1573Gly (c.4717A>G) in the general population?

DOCK7 p.Ser1573Gly (c.4717A>G) is ultra-rare (popmax 0.0822%, mid) (gnomAD).

What do computational predictors say about DOCK7 p.Ser1573Gly (c.4717A>G)?

AlphaMissense predicts ambiguous (score 0.4149) — an in-silico prediction, not a clinical call.

DOCK7 p.Ser1573Gly

c.4717A>G · rs376119113 · VCV582554

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4149 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0822%, mid)

Conditions

developmental and epileptic encephalopathy, 23

Computational evidence

Protein change
AlphaMissense	0.4149	ambiguous
REVEL	0.376	indeterminate
SaProt	LLR -10.75	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.51	GERP -2.4, phastCons 0.09
Regional constraint	o/e 0.71	unconstrained · MANE · 58 kb · p 5.9e-19 · regional, not allelic
Overall
CADD	22.0	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 0.0822% Middle Eastern · 5/6,084 alleles

Filtering AF 0.0323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00297% 48/1,613,976 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0822%	1,217
African / African-American	0.0187%	5,352
Remaining individualsnot grpmax-eligible	0.0176%	5,680
Admixed American	0.00333%	29,993
European (non-Finnish)	0.00127%	78,667
South Asian	0.0011%	91,056

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.Ser1573Gly
Coding: c.4717A>G
MANE Select: NM_001367561
dbSNP: rs376119113
Type: single nucleotide variant
Location: chr1:62504677 (GRCh38)
Gene constraint: LOEUF 0.551 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 2 PDB

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 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-ser1573gly (accessed [today's date]).

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