Is DOCK2 c.321+87C>T pathogenic?

DOCK2 c.321+87C>T is classified Benign in DOCK2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-01-24). Common (popmax 30.2%, sas) — too common for a highly-penetrant pathogenic allele.

DOCK2 c.321+87C>T

Q: How common is DOCK2 c.321+87C>T in the general population?

DOCK2 c.321+87C>T is common (popmax 30.2%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs12656761 · VCV2688329

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 30.2%, sas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
Splice region	donor +87	deep intronic (+87 nt into the intron)
SpliceAI	Δ0.68	donor gain · deltas
Pangolin	Δ0.56	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -1.5	GERP -3.5
Non-coding constraint	Z 3.49	1 kb window · o/e 0.75 · regional · uncalibrated
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.2% South Asian · 23,962/79,240 alleles

Filtering AF 29.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 29.8%

Overall 23.6% 295,093/1,250,614 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	31.5%	3
South Asiangrpmax	30.2%	3
East Asian	29.3%	3
European (non-Finnish)	24.6%	4
Middle Eastern	23.8%	4
Remaining individualsnot grpmax-eligible	23.6%	4
Finnishnot grpmax-eligible	21.5%	5
Ashkenazi Jewishnot grpmax-eligible	19.9%	5
Admixed American	14.4%	7
African / African-American	10.2%	10

Amish 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: DOCK2
Coding: c.321+87C>T
MANE Select: NM_004946
dbSNP: rs12656761
Type: single nucleotide variant
Location: chr5:169671261 (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

Similar variants

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
DOCK2 p.Ala24Pro Uncertain significance ★★ ⚠ same type
DOCK2 p.Ala454Val 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-c-321-plus-87c-t (accessed [today's date]).

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