Is DOCK10 p.Met645Val (c.1933A>G) pathogenic?

DOCK10 p.Met645Val (c.1933A>G) is classified Uncertain significance in DOCK10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). AlphaMissense: likely benign (0.0687); Very rare (popmax 0.00334%, amr).

How common is DOCK10 p.Met645Val (c.1933A>G) in the general population?

DOCK10 p.Met645Val (c.1933A>G) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about DOCK10 p.Met645Val (c.1933A>G)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

DOCK10 p.Met645Val

c.1933A>G · VCV3504366

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -6.14	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 0.93	GERP -2.2, phastCons 0.009
Regional constraint	o/e 0.97	unconstrained · MANE · 219 kb · p 0.24 · regional, not allelic
Overall
CADD	9.954	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 0.00334% Admixed American · 2/59,800 alleles

Filtering AF 0.000555% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000684% 11/1,608,506 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,900
Remaining individualsnot grpmax-eligible	0.00161%	62,184
European (non-Finnish)	0.00068%	147,061

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: DOCK10
Protein: p.Met645Val
Coding: c.1933A>G
MANE Select: NM_014689
Type: single nucleotide variant
Location: chr2:224853078 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.47 · 4 PDB

Full DOCK10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK10 p.Asp2034= Benign ★★ same type
DOCK10 p.Ser1349= Benign ★★ same type
DOCK10 p.Thr1950= Benign ★★ same type
DOCK10 p.Ala112Ser Uncertain significance ★ ⚠ same type
DOCK10 p.Ala1135Thr Uncertain significance ★ ⚠ same type
DOCK10 p.Ala1175Thr Uncertain significance ★ ⚠ same type
DOCK10 p.Ala1177Ser Uncertain significance ★ ⚠ same type
DOCK10 p.Ala1271Glu 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/dock10-p-met645val (accessed [today's date]).

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