Is DOCK7 p.Val19Ile (c.55G>A) pathogenic?

DOCK7 p.Val19Ile (c.55G>A) is classified Uncertain significance in DOCK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-13). AlphaMissense: ambiguous (0.563); Very rare (popmax 0.00334%, amr); Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Val19Ile (c.55G>A)?

DOCK7 p.Val19Ile (c.55G>A) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

How common is DOCK7 p.Val19Ile (c.55G>A) in the general population?

DOCK7 p.Val19Ile (c.55G>A) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about DOCK7 p.Val19Ile (c.55G>A)?

AlphaMissense predicts ambiguous (score 0.563) — an in-silico prediction, not a clinical call.

DOCK7 p.Val19Ile

c.55G>A · rs770149679 · VCV1976586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.563 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

developmental and epileptic encephalopathy, 23

Computational evidence

Protein change
AlphaMissense	0.563	ambiguous
REVEL	0.084	moderately benign-leaning
SaProt	LLR -6.75	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 175 kb · p 3.6e-10 · regional, not allelic
Overall
CADD	25.7	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 0.00334% Admixed American · 2/59,876 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000806% 13/1,612,154 alleles · very rare exomes 12/1,460,508 · genomes 1/151,646 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,938
Remaining individualsnot grpmax-eligible	0.0016%	62,398
European (non-Finnish)	0.000848%	117,926

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.Val19Ile
Coding: c.55G>A
MANE Select: NM_001367561
dbSNP: rs770149679
Type: single nucleotide variant
Location: chr1:62663114 (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-val19ile (accessed [today's date]).

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