Is DOCK2 p.Asp341Glu (c.1023T>G) pathogenic?

DOCK2 p.Asp341Glu (c.1023T>G) is classified Uncertain significance in DOCK2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-06-10). AlphaMissense: ambiguous (0.5144); Ultra-rare (popmax 0.044%, afr); Associated with Inborn genetic diseases.

What condition is associated with DOCK2 p.Asp341Glu (c.1023T>G)?

DOCK2 p.Asp341Glu (c.1023T>G) is associated with Inborn genetic diseases, DOCK2 deficiency (ClinVar).

How common is DOCK2 p.Asp341Glu (c.1023T>G) in the general population?

DOCK2 p.Asp341Glu (c.1023T>G) is ultra-rare (popmax 0.044%, afr) (gnomAD).

What do computational predictors say about DOCK2 p.Asp341Glu (c.1023T>G)?

AlphaMissense predicts ambiguous (score 0.5144) — an in-silico prediction, not a clinical call.

DOCK2 p.Asp341Glu

c.1023T>G · rs368378335 · VCV955751

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5144 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.044%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5144	ambiguous
REVEL	0.242	benign-leaning
SaProt	LLR -8.23	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 -2.5	GERP -4.5
Regional constraint	o/e 0.73	unconstrained · MANE · 63 kb · p 1.8e-09 · regional, not allelic
Overall
CADD	17.52	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 0.044% African / African-American · 33/74,950 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0281%

Overall 0.00211% 34/1,614,010 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.044%	2,271
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Asp341Glu
Coding: c.1023T>G
MANE Select: NM_004946
dbSNP: rs368378335
Type: single nucleotide variant
Location: chr5:169698417 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB

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-asp341glu (accessed [today's date]).

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