Is DOCK9 p.Ala1494Val (c.4481C>T) pathogenic?

DOCK9 p.Ala1494Val (c.4481C>T) is classified Uncertain significance in DOCK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-18). AlphaMissense: ambiguous (0.4949); Very rare (popmax 0.0094%, afr).

How common is DOCK9 p.Ala1494Val (c.4481C>T) in the general population?

DOCK9 p.Ala1494Val (c.4481C>T) is very rare (popmax 0.0094%, afr) (gnomAD).

What do computational predictors say about DOCK9 p.Ala1494Val (c.4481C>T)?

AlphaMissense predicts ambiguous (score 0.4949) — an in-silico prediction, not a clinical call.

DOCK9 p.Ala1494Val

c.4481C>T · rs776321246 · VCV2290061

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4949 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0094%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4949	ambiguous
REVEL	0.203	benign-leaning
SaProt	LLR -2.70	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 43 kb · p 1.3e-16 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A1472V vs ClinVar A1494V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0094% African / African-American · 7/74,442 alleles

Filtering AF 0.0044% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00157% 25/1,588,188 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0094%	10,635
Admixed American	0.00359%	27,861
Remaining individualsnot grpmax-eligible	0.00162%	61,656
European (non-Finnish)	0.0012%	83,341
South Asian	0.00115%	86,996

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.Ala1494Val
Coding: c.4481C>T
MANE Select: NM_001366683
dbSNP: rs776321246
Type: single nucleotide variant
Location: chr13:98831502 (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-ala1494val (accessed [today's date]).

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