Is DOCK9 p.Pro316Leu (c.947C>T) pathogenic?

DOCK9 p.Pro316Leu (c.947C>T) is classified Uncertain significance in DOCK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.1238); Ultra-rare (popmax 0.0165%, mid).

How common is DOCK9 p.Pro316Leu (c.947C>T) in the general population?

DOCK9 p.Pro316Leu (c.947C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DOCK9 p.Pro316Leu (c.947C>T)?

AlphaMissense predicts likely benign (score 0.1238) — an in-silico prediction, not a clinical call.

DOCK9 p.Pro316Leu

c.947C>T · VCV4244083

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1238 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1238	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -5.60	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	24.7	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 P317L vs ClinVar P316L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,076 alleles

Filtering AF 0.000891% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000447%

Overall 0.000932% 15/1,608,698 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,076
South Asian	0.00335%	29,814
Remaining individualsnot grpmax-eligible	0.00161%	62,300
African / African-American	0.00134%	74,814
European (non-Finnish)	0.000764%	130,868

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.Pro316Leu
Coding: c.947C>T
MANE Select: NM_001366683
Type: single nucleotide variant
Location: chr13:98914341 (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-pro316leu (accessed [today's date]).

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