Is DOCK7 p.Ile919Phe (c.2755A>T) pathogenic?

DOCK7 p.Ile919Phe (c.2755A>T) is classified Uncertain significance in DOCK7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-11). AlphaMissense: ambiguous (0.4328); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with DOCK7 p.Ile919Phe (c.2755A>T)?

DOCK7 p.Ile919Phe (c.2755A>T) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK7 p.Ile919Phe (c.2755A>T) in the general population?

DOCK7 p.Ile919Phe (c.2755A>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DOCK7 p.Ile919Phe (c.2755A>T)?

AlphaMissense predicts ambiguous (score 0.4328) — an in-silico prediction, not a clinical call.

DOCK7 p.Ile919Phe

c.2755A>T · VCV3504547

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4328 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4328	ambiguous
REVEL	0.406	indeterminate
SaProt	LLR -5.77	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.8, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 175 kb · p 3.6e-10 · regional, not allelic
Overall
CADD	23.7	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 0.0011% South Asian · 1/90,616 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,611,636 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,616
European (non-Finnish)	0.000424%	235,747

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.Ile919Phe
Coding: c.2755A>T
MANE Select: NM_001367561
Type: single nucleotide variant
Location: chr1:62552743 (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 919: 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

Similar variants

DOCK7 p.Ile919Thr Uncertain significance ★ ⚠ same residue
DOCK7 p.Ile919Val Uncertain significance ★ ⚠ same residue
DOCK7 p.Ile919= Likely benign ★ same residue
DOCK7 c.3781+4C>G Uncertain significance ★★ same condition
DOCK7 p.Ala1479Thr Uncertain significance ★★ ⚠ same condition
DOCK7 p.Ala205Thr Uncertain significance ★★ ⚠ same condition
DOCK7 p.Arg1266Gln Uncertain significance ★★ ⚠ same condition
DOCK7 p.Arg1358Gln 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-ile919phe (accessed [today's date]).

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