Is DOCK3 p.Leu99= (c.295T>C) pathogenic?

DOCK3 p.Leu99= (c.295T>C) is classified Likely benign in DOCK3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-25). Rare (popmax 0.628%, afr); Associated with DOCK3-related disorder.

What condition is associated with DOCK3 p.Leu99= (c.295T>C)?

DOCK3 p.Leu99= (c.295T>C) is associated with DOCK3-related disorder (ClinVar).

How common is DOCK3 p.Leu99= (c.295T>C) in the general population?

DOCK3 p.Leu99= (c.295T>C) is rare (popmax 0.628%, afr) (gnomAD).

DOCK3 p.Leu99=

c.295T>C · rs144781090 · VCV3048862

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.628%, afr)

Conditions

DOCK3-related disorder

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 0.59	GERP -0.91, phastCons 1
Overall
CADD	8.169	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.628% African / African-American · 471/75,028 alleles

Filtering AF 0.581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.562%

Overall 0.0323% 521/1,610,560 alleles · rare exomes 232/1,458,216 · genomes 289/152,344 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.628%	159
Middle Eastern	0.132%	756
Admixed American	0.0469%	2,132
Remaining individualsnot grpmax-eligible	0.0208%	4,796
European (non-Finnish)	8.49e-05%	1,178,089

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.Leu99=
Coding: c.295T>C
MANE Select: NM_004947
dbSNP: rs144781090
Type: single nucleotide variant
Location: chr3:50934057 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.52

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

Disease context

DOCK3-related disorder

Similar variants

DOCK3 p.Leu99Phe Uncertain significance ★ ⚠ same residue
DOCK3 c.1037+1G>A Likely pathogenic ★ same condition
DOCK3 p.Arg362Ter Likely pathogenic ★ same condition
DOCK3 c.2548+6T>A Benign same condition
DOCK3 c.3915+10A>G Likely benign same condition
DOCK3 c.5412+10C>T Likely benign same condition
DOCK3 p.Asp1841= Likely benign same condition
DOCK3 p.Asp676= Likely benign 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-leu99 (accessed [today's date]).

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