Is DOCK3 p.Leu612Val (c.1834C>G) pathogenic?

DOCK3 p.Leu612Val (c.1834C>G) is classified Uncertain significance in DOCK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-06). AlphaMissense: ambiguous (0.3787); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DOCK3 p.Leu612Val (c.1834C>G)?

DOCK3 p.Leu612Val (c.1834C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK3 p.Leu612Val (c.1834C>G) in the general population?

DOCK3 p.Leu612Val (c.1834C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOCK3 p.Leu612Val (c.1834C>G)?

AlphaMissense predicts ambiguous (score 0.3787) — an in-silico prediction, not a clinical call.

DOCK3 p.Leu612Val

c.1834C>G · rs373320886 · VCV3084988

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3787 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3787	ambiguous
REVEL	0.273	benign-leaning
SaProt	LLR -10.18	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.67	GERP -0.41, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 154 kb · p 4e-32 · regional, not allelic
Overall
CADD	22.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DOCK3
Protein: p.Leu612Val
Coding: c.1834C>G
MANE Select: NM_004947
dbSNP: rs373320886
Type: single nucleotide variant
Location: chr3:51229526 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.52
Residue 612: a UniProt-annotated variant site (in nedidha)

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-leu612val (accessed [today's date]).

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