Is DOCK5 p.Pro1096Ser (c.3286C>T) pathogenic?

DOCK5 p.Pro1096Ser (c.3286C>T) is classified Uncertain significance in DOCK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely benign (0.1469); Very rare (popmax 0.00761%, nfe).

How common is DOCK5 p.Pro1096Ser (c.3286C>T) in the general population?

DOCK5 p.Pro1096Ser (c.3286C>T) is very rare (popmax 0.00761%, nfe) (gnomAD).

What do computational predictors say about DOCK5 p.Pro1096Ser (c.3286C>T)?

AlphaMissense predicts likely benign (score 0.1469) — an in-silico prediction, not a clinical call.

DOCK5 p.Pro1096Ser

c.3286C>T · rs139729836 · VCV2344012

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1469 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00761%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1469	likely benign
REVEL	0.255	benign-leaning
SaProt	LLR -6.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 107 kb · p 5.5e-05 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00761% European (non-Finnish) · 89/1,169,656 alleles

Filtering AF 0.00628% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00584%

Overall 0.00572% 91/1,591,324 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00761%	13,142
Admixed American	0.0018%	55,552
Remaining individualsnot grpmax-eligible	0.00162%	61,546

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: DOCK5
Protein: p.Pro1096Ser
Coding: c.3286C>T
MANE Select: NM_024940
dbSNP: rs139729836
Type: single nucleotide variant
Location: chr8:25368573 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.63 · 11 PDB

Full DOCK5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK5 c.4788+9C>T Benign ★★ same type
DOCK5 p.Leu986Phe Benign/Likely benign ★★ same type
DOCK5 p.Met987Leu Benign ★★ same type
DOCK5 p.Pro1467= Benign ★★ same type
DOCK5 p.Ser1306= Benign ★★ same type
DOCK5 p.Thr469Met Benign/Likely benign ★★ ⚠ same type
DOCK5 p.Ala1067Val Uncertain significance ★ ⚠ same type
DOCK5 p.Ala1194Ser 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/dock5-p-pro1096ser (accessed [today's date]).

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