Is DOCK9 p.Ala434Val (c.1301C>T) pathogenic?

DOCK9 p.Ala434Val (c.1301C>T) is classified Benign in DOCK9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2016-03-29). AlphaMissense: likely benign (0.0739); Common (popmax 8.66%, sas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DOCK9 p.Ala434Val (c.1301C>T)?

AlphaMissense predicts likely benign (score 0.0739) — an in-silico prediction, not a clinical call.

DOCK9 p.Ala434Val

Q: How common is DOCK9 p.Ala434Val (c.1301C>T) in the general population?

DOCK9 p.Ala434Val (c.1301C>T) is common (popmax 8.66%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1301C>T · rs62620184 · VCV402794

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0739 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.66%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0739	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -7.09	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 2.7	GERP 0.7, phastCons 0.12
Regional constraint	o/e 0.87	unconstrained · MANE · 140 kb · p 1.2e-07 · regional, not allelic
Overall
CADD	14.16	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 A435V vs ClinVar A434V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.66% South Asian · 7,890/91,074 alleles

Filtering AF 8.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.44%

Overall 4.37% 70,541/1,613,954 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	8.66%	12
Middle Eastern	8.63%	12
Ashkenazi Jewishnot grpmax-eligible	5.34%	19
Amishnot grpmax-eligible	5.26%	19
Remaining individualsnot grpmax-eligible	4.53%	22
European (non-Finnish)	4.47%	22
Finnishnot grpmax-eligible	3.92%	25
Admixed American	2.89%	35
African / African-American	0.862%	116
East Asian	0.0557%	1,795

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.Ala434Val
Coding: c.1301C>T
MANE Select: NM_001366683
dbSNP: rs62620184
Type: single nucleotide variant
Location: chr13:98902367 (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.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
DOCK9 p.Ala100Ser 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-ala434val (accessed [today's date]).

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