Is DOCK5 p.Pro1817Thr (c.5449C>A) pathogenic?

DOCK5 p.Pro1817Thr (c.5449C>A) is classified Uncertain significance in DOCK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). AlphaMissense: likely benign (0.1522); Very rare (popmax 0.00446%, eas).

How common is DOCK5 p.Pro1817Thr (c.5449C>A) in the general population?

DOCK5 p.Pro1817Thr (c.5449C>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DOCK5 p.Pro1817Thr (c.5449C>A)?

AlphaMissense predicts likely benign (score 0.1522) — an in-silico prediction, not a clinical call.

DOCK5 p.Pro1817Thr

c.5449C>A · VCV3273374

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1522 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1522	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -8.93	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 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 107 kb · p 5.5e-05 · regional, not allelic
Overall
CADD	22.1	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,796 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000137% 2/1,461,136 alleles · very rare

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.Pro1817Thr
Coding: c.5449C>A
MANE Select: NM_024940
Type: single nucleotide variant
Location: chr8:25410143 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.63 · 11 PDB
Residue 1817: the 'disordered' region

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-pro1817thr (accessed [today's date]).

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