Is DOCK9 p.Thr431= (c.1293G>A) pathogenic?

DOCK9 p.Thr431= (c.1293G>A) is classified Likely benign in DOCK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-01). Rare (popmax 0.576%, nfe).

How common is DOCK9 p.Thr431= (c.1293G>A) in the general population?

DOCK9 p.Thr431= (c.1293G>A) is rare (popmax 0.576%, nfe) (gnomAD).

DOCK9 p.Thr431=

c.1293G>A · rs142267943 · VCV2643888

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.576%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -5
Overall
CADD	0.053	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.576% European (non-Finnish) · 6,800/1,179,868 alleles

Filtering AF 0.565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.56%

Overall 0.49% 7,907/1,613,974 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.63%	38
Finnishnot grpmax-eligible	0.87%	115
European (non-Finnish)grpmax	0.576%	174
Remaining individualsnot grpmax-eligible	0.397%	252
Admixed American	0.168%	594
African / African-American	0.104%	962
South Asian	0.0845%	1,183
Ashkenazi Jewishnot grpmax-eligible	0.0473%	2,115
Middle Eastern	0.033%	3,031
East Asian	0.0134%	7,479

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: DOCK9
Protein: p.Thr431=
Coding: c.1293G>A
MANE Select: NM_001366683
dbSNP: rs142267943
Type: single nucleotide variant
Location: chr13:98902375 (GRCh38)
Gene constraint: LOEUF 0.425 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68 · 4 PDB

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-thr431 (accessed [today's date]).

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