Is DOCK2 p.Arg36Ter (c.106C>T) pathogenic?

DOCK2 p.Arg36Ter (c.106C>T) is classified Likely pathogenic in DOCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-16). Very rare (popmax 8.47e-05%, nfe).

How common is DOCK2 p.Arg36Ter (c.106C>T) in the general population?

DOCK2 p.Arg36Ter (c.106C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

DOCK2 p.Arg36Ter

c.106C>T · VCV3910720

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 52
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -0.068, phastCons 0.82
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,024 alleles

Overall 6.84e-05% 1/1,461,826 alleles · very rare

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: DOCK2
Protein: p.Arg36Ter
Coding: c.106C>T
MANE Select: NM_004946
Type: single nucleotide variant
Location: chr5:169654465 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB
Residue 36: the sh3 domain; a β-strand

Full DOCK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK2 p.Arg36Gln Uncertain significance ★ ⚠ same residue
INSYN2B p.Gln36Pro Uncertain significance ★ ⚠ same residue
DOCK2 c.2267+3G>A Uncertain significance ★★ same type
DOCK2 c.2704-3C>T Uncertain significance ★★ same type
DOCK2 c.4467+4A>G Uncertain significance ★★ same type
DOCK2 p.Ala1393Val Uncertain significance ★★ ⚠ same type
DOCK2 p.Ala1710Val Uncertain significance ★★ ⚠ same type
DOCK2 p.Ala1765Val 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/dock2-p-arg36ter (accessed [today's date]).

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