Is DOCK9 p.Ser782Leu (c.2345C>T) pathogenic?

DOCK9 p.Ser782Leu (c.2345C>T) is classified Uncertain significance in DOCK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-17). AlphaMissense: likely benign (0.0715); Rare (popmax 0.223%, afr).

How common is DOCK9 p.Ser782Leu (c.2345C>T) in the general population?

DOCK9 p.Ser782Leu (c.2345C>T) is rare (popmax 0.223%, afr) (gnomAD).

What do computational predictors say about DOCK9 p.Ser782Leu (c.2345C>T)?

AlphaMissense predicts likely benign (score 0.0715) — an in-silico prediction, not a clinical call.

DOCK9 p.Ser782Leu

c.2345C>T · VCV4014275

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0715 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.223%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0715	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -5.78	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 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 140 kb · p 1.2e-07 · regional, not allelic
Overall
CADD	24.1	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S783L vs ClinVar S782L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.223% African / African-American · 167/74,998 alleles

Filtering AF 0.195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.184%

Overall 0.0134% 217/1,613,626 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.223%	449
Admixed American	0.0383%	2,608
Remaining individualsnot grpmax-eligible	0.0128%	7,809
East Asian	0.00446%	22,436
South Asian	0.0022%	45,498
Finnishnot grpmax-eligible	0.00156%	64,002
European (non-Finnish)	0.00119%	84,268

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: DOCK9
Protein: p.Ser782Leu
Coding: c.2345C>T
MANE Select: NM_001366683
Type: single nucleotide variant
Location: chr13:98885008 (GRCh38)
Gene constraint: LOEUF 0.425 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68 · 4 PDB
Residue 782: the c2 dock-type domain

Full DOCK9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK9 p.Ala434Val Benign ★★ same type
DOCK9 p.Asn1709= Benign ★★ same type
DOCK9 p.Cys2012= Benign/Likely benign ★★ same type
DOCK9 p.Leu1435= Benign ★★ same type
DOCK9 c.5023+908C>T Uncertain significance ★ ⚠ same type
DOCK9 c.5023+919C>T Uncertain significance ★ ⚠ same type
DOCK9 c.5023+952C>T Uncertain significance ★ ⚠ same type
DOCK9 c.5367+706T>A 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/dock9-p-ser782leu (accessed [today's date]).

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