Is DOCK3 p.Val1448Ile (c.4342G>A) pathogenic?

DOCK3 p.Val1448Ile (c.4342G>A) is classified Uncertain significance in DOCK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.1314); Ultra-rare (popmax 0.0136%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DOCK3 p.Val1448Ile (c.4342G>A)?

DOCK3 p.Val1448Ile (c.4342G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK3 p.Val1448Ile (c.4342G>A) in the general population?

DOCK3 p.Val1448Ile (c.4342G>A) is ultra-rare (popmax 0.0136%, nfe) (gnomAD).

What do computational predictors say about DOCK3 p.Val1448Ile (c.4342G>A)?

AlphaMissense predicts likely benign (score 0.1314) — an in-silico prediction, not a clinical call.

DOCK3 p.Val1448Ile

c.4342G>A · VCV4014114

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1314 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0136%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1314	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 154 kb · p 4e-32 · regional, not allelic
Overall
CADD	23.5	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 0.0136% European (non-Finnish) · 161/1,179,890 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0113%

Overall 0.0114% 166/1,461,702 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0136%	7,329
Remaining individualsnot grpmax-eligible	0.0048%	20,829
East Asian	0.00223%	44,888
South Asian	0.0011%	91,080

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: DOCK3
Protein: p.Val1448Ile
Coding: c.4342G>A
MANE Select: NM_004947
Type: single nucleotide variant
Location: chr3:51356181 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.52
Residue 1448: a UniProt-annotated variant site (in nedidha); the docker domain

Full DOCK3 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

DOCK3 p.Arg1609Trp Uncertain significance ★★ ⚠ same condition
DOCK3 p.Arg1787Gln Uncertain significance ★★ ⚠ same condition
DOCK3 p.Arg2020Cys Uncertain significance ★★ ⚠ same condition
DOCK3 p.Arg392Gln Uncertain significance ★★ ⚠ same condition
DOCK3 p.Arg486His Uncertain significance ★★ ⚠ same condition
DOCK3 p.Gly1699Cys Uncertain significance ★★ ⚠ same condition
DOCK3 p.Leu1982Arg Uncertain significance ★★ ⚠ same condition
DOCK3 p.Lys343Arg 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/dock3-p-val1448ile (accessed [today's date]).

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