Is DOCK3 p.Leu1279= (c.3837C>T) pathogenic?

DOCK3 p.Leu1279= (c.3837C>T) is classified Likely benign in DOCK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). Very rare (popmax 8.48e-05%, nfe).

How common is DOCK3 p.Leu1279= (c.3837C>T) in the general population?

DOCK3 p.Leu1279= (c.3837C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

DOCK3 p.Leu1279=

c.3837C>T · VCV4535052

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -4.1
Overall
CADD	5.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,396 alleles

Overall 0.000137% 2/1,460,700 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,436
European (non-Finnish)grpmax	8.48e-05%	1,179,395

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu1279=
Coding: c.3837C>T
MANE Select: NM_004947
Type: single nucleotide variant
Location: chr3:51341307 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.52
Residue 1279: a UniProt-annotated variant site (in nedidha); the docker domain

Full DOCK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK3 p.Leu1279Phe Uncertain significance ★ ⚠ same residue
DOCK3 p.Arg1609Trp Uncertain significance ★★ ⚠ same type
DOCK3 p.Arg1787Gln Uncertain significance ★★ ⚠ same type
DOCK3 p.Arg2020Cys Uncertain significance ★★ ⚠ same type
DOCK3 p.Arg392Gln Uncertain significance ★★ ⚠ same type
DOCK3 p.Arg486His Uncertain significance ★★ ⚠ same type
DOCK3 p.Gly1699Cys Uncertain significance ★★ ⚠ same type
DOCK3 p.Leu1982Arg Uncertain significance ★★ ⚠ same type

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-leu1279 (accessed [today's date]).

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