Is DOCK2 p.Ile152Val (c.454A>G) pathogenic?

DOCK2 p.Ile152Val (c.454A>G) is classified Uncertain significance in DOCK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-31). AlphaMissense: ambiguous (0.3859); Ultra-rare (popmax 0.0714%, sas); Associated with Inborn genetic diseases.

What condition is associated with DOCK2 p.Ile152Val (c.454A>G)?

DOCK2 p.Ile152Val (c.454A>G) is associated with Inborn genetic diseases, DOCK2 deficiency (ClinVar).

How common is DOCK2 p.Ile152Val (c.454A>G) in the general population?

DOCK2 p.Ile152Val (c.454A>G) is ultra-rare (popmax 0.0714%, sas) (gnomAD).

What do computational predictors say about DOCK2 p.Ile152Val (c.454A>G)?

AlphaMissense predicts ambiguous (score 0.3859) — an in-silico prediction, not a clinical call.

DOCK2 p.Ile152Val

c.454A>G · rs761361714 · VCV2420389

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3859 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0714%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3859	ambiguous
REVEL	0.267	benign-leaning
SaProt	LLR -9.61	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 63 kb · p 1.8e-09 · regional, not allelic
Overall
CADD	25.0	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

Grpmax group 0.0714% South Asian · 65/91,080 alleles

Filtering AF 0.0574% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.00421% 68/1,613,998 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0714%	1,401
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)	8.47e-05%	1,179,990

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.Ile152Val
Coding: c.454A>G
MANE Select: NM_004946
dbSNP: rs761361714
Type: single nucleotide variant
Location: chr5:169674429 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB
Residue 152: an α-helix

Full DOCK2 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

Also linked: DOCK2 deficiency

Similar variants

DOCK2 c.2267+3G>A Uncertain significance ★★ same condition
DOCK2 c.2704-3C>T Uncertain significance ★★ same condition
DOCK2 c.4467+4A>G Uncertain significance ★★ same condition
DOCK2 p.Ala1393Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala1710Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala1765Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala24Pro Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala454Val 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/dock2-p-ile152val (accessed [today's date]).

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