Is DOCK9 p.Ala98Val (c.293C>T) pathogenic?

DOCK9 p.Ala98Val (c.293C>T) is classified Uncertain significance in DOCK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.086); Very rare (popmax 0.00873%, nfe).

How common is DOCK9 p.Ala98Val (c.293C>T) in the general population?

DOCK9 p.Ala98Val (c.293C>T) is very rare (popmax 0.00873%, nfe) (gnomAD).

What do computational predictors say about DOCK9 p.Ala98Val (c.293C>T)?

AlphaMissense predicts likely benign (score 0.086) — an in-silico prediction, not a clinical call.

DOCK9 p.Ala98Val

c.293C>T · rs775087973 · VCV3085126

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.086 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00873%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.086	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.87	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 -0.005	GERP -5
Regional constraint	o/e 0.87	unconstrained · MANE · 140 kb · p 1.2e-07 · regional, not allelic
Overall
CADD	11.66	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 A99V vs ClinVar A98V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00873% European (non-Finnish) · 103/1,179,168 alleles

Filtering AF 0.00733% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00684%

Overall 0.00713% 115/1,612,070 alleles · very rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.11%	912
European (non-Finnish)grpmax	0.00873%	11,448
Admixed American	0.00669%	14,949
Remaining individualsnot grpmax-eligible	0.00641%	15,607
South Asian	0.00221%	45,178
Finnishnot grpmax-eligible	0.00156%	63,956

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.Ala98Val
Coding: c.293C>T
MANE Select: NM_001366683
dbSNP: rs775087973
Type: single nucleotide variant
Location: chr13:98930208 (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-ala98val (accessed [today's date]).

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