Is DOCK7 p.Ser970Gly (c.2908A>G) pathogenic?

DOCK7 p.Ser970Gly (c.2908A>G) is classified Uncertain significance in DOCK7 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-02-26). AlphaMissense: likely benign (0.1972); Ultra-rare (popmax 0.0538%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DOCK7 p.Ser970Gly (c.2908A>G)?

DOCK7 p.Ser970Gly (c.2908A>G) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Ser970Gly (c.2908A>G) in the general population?

DOCK7 p.Ser970Gly (c.2908A>G) is ultra-rare (popmax 0.0538%, nfe) (gnomAD).

What do computational predictors say about DOCK7 p.Ser970Gly (c.2908A>G)?

AlphaMissense predicts likely benign (score 0.1972) — an in-silico prediction, not a clinical call.

DOCK7 p.Ser970Gly

c.2908A>G · rs199681303 · VCV434959

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1972 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0538%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1972	likely benign
REVEL	0.364	indeterminate
SaProt	LLR -7.06	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.24	acceptor loss, 48 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 175 kb · p 3.6e-10 · regional, not allelic
Overall
CADD	24.0	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 0.0538% European (non-Finnish) · 632/1,173,788 alleles

Filtering AF 0.0503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0489%

Overall 0.0409% 657/1,605,674 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0538%	1,857
African / African-American	0.0187%	5,354
Remaining individualsnot grpmax-eligible	0.0113%	8,871
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,376
Admixed American	0.00334%	29,958
South Asian	0.00111%	90,070

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.Ser970Gly
Coding: c.2908A>G
MANE Select: NM_001367561
dbSNP: rs199681303
Type: single nucleotide variant
Location: chr1:62543697 (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 970: the 'disordered' region

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 p.Ser970Arg 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-ser970gly (accessed [today's date]).

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