Is DOCK9 p.Val1071Ala (c.3212T>C) pathogenic?

DOCK9 p.Val1071Ala (c.3212T>C) is classified Uncertain significance in DOCK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: ambiguous (0.4667); Very rare (popmax 0.00336%, amr).

How common is DOCK9 p.Val1071Ala (c.3212T>C) in the general population?

DOCK9 p.Val1071Ala (c.3212T>C) is very rare (popmax 0.00336%, amr) (gnomAD).

What do computational predictors say about DOCK9 p.Val1071Ala (c.3212T>C)?

AlphaMissense predicts ambiguous (score 0.4667) — an in-silico prediction, not a clinical call.

DOCK9 p.Val1071Ala

c.3212T>C · VCV4244078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4667 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00336%, amr)

Computational evidence

Protein change
AlphaMissense	0.4667	ambiguous
REVEL	0.629	indeterminate
SaProt	LLR -8.69	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.66 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 140 kb · p 1.2e-07 · regional, not allelic
Overall
CADD	23.6	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 V1072A vs ClinVar V1071A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00336% Admixed American · 2/59,564 alleles

Filtering AF 0.00232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00298% 48/1,611,950 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00938%	10,660
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,566
Admixed Americangrpmax	0.00336%	29,782
Remaining individualsnot grpmax-eligible	0.00321%	31,183
European (non-Finnish)	0.00314%	31,869

Finnish 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.Val1071Ala
Coding: c.3212T>C
MANE Select: NM_001366683
Type: single nucleotide variant
Location: chr13:98867499 (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-val1071ala (accessed [today's date]).

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