Is DOCK5 p.Val552Met (c.1654G>A) pathogenic?

DOCK5 p.Val552Met (c.1654G>A) is classified Uncertain significance in DOCK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.2114); Ultra-rare (popmax 0.033%, mid).

How common is DOCK5 p.Val552Met (c.1654G>A) in the general population?

DOCK5 p.Val552Met (c.1654G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about DOCK5 p.Val552Met (c.1654G>A)?

AlphaMissense predicts likely benign (score 0.2114) — an in-silico prediction, not a clinical call.

DOCK5 p.Val552Met

c.1654G>A · VCV3273353

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2114 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2114	likely benign
REVEL	0.563	indeterminate
SaProt	LLR -9.49	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 107 kb · p 5.5e-05 · regional, not allelic
Overall
CADD	28.9	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 0.033% Middle Eastern · 2/6,060 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00242% 39/1,613,518 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,030
Remaining individualsnot grpmax-eligible	0.0064%	15,619
European (non-Finnish)	0.00271%	36,866
Admixed American	0.00167%	59,972

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.Val552Met
Coding: c.1654G>A
MANE Select: NM_024940
Type: single nucleotide variant
Location: chr8:25323886 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.63 · 11 PDB
Residue 552: the c2 dock-type domain

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-val552met (accessed [today's date]).

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