Is DOCK5 p.Pro434Ala (c.1300C>G) pathogenic?

DOCK5 p.Pro434Ala (c.1300C>G) is classified Uncertain significance in DOCK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-23). AlphaMissense: ambiguous (0.3942); Ultra-rare (popmax 0.0132%, sas).

How common is DOCK5 p.Pro434Ala (c.1300C>G) in the general population?

DOCK5 p.Pro434Ala (c.1300C>G) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

What do computational predictors say about DOCK5 p.Pro434Ala (c.1300C>G)?

AlphaMissense predicts ambiguous (score 0.3942) — an in-silico prediction, not a clinical call.

DOCK5 p.Pro434Ala

c.1300C>G · VCV4014171

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3942 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Computational evidence

Protein change
AlphaMissense	0.3942	ambiguous
REVEL	0.548	indeterminate
SaProt	LLR -7.12	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 107 kb · p 5.5e-05 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0132% South Asian · 12/90,662 alleles

Filtering AF 0.00754% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00595%

Overall 0.000869% 14/1,611,612 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,555
Remaining individualsnot grpmax-eligible	0.00321%	31,193

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: DOCK5
Protein: p.Pro434Ala
Coding: c.1300C>G
MANE Select: NM_024940
Type: single nucleotide variant
Location: chr8:25310514 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.63 · 11 PDB

Full DOCK5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK5 c.4788+9C>T Benign ★★ same type
DOCK5 p.Leu986Phe Benign/Likely benign ★★ same type
DOCK5 p.Met987Leu Benign ★★ same type
DOCK5 p.Pro1467= Benign ★★ same type
DOCK5 p.Ser1306= Benign ★★ same type
DOCK5 p.Thr469Met Benign/Likely benign ★★ ⚠ same type
DOCK5 p.Ala1067Val Uncertain significance ★ ⚠ same type
DOCK5 p.Ala1194Ser 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/dock5-p-pro434ala (accessed [today's date]).

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