Is DOCK10 p.Gly173Val (c.518G>T) pathogenic?

DOCK10 p.Gly173Val (c.518G>T) is classified Uncertain significance in DOCK10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-23). AlphaMissense: ambiguous (0.4001); Ultra-rare (popmax 0.0164%, mid).

How common is DOCK10 p.Gly173Val (c.518G>T) in the general population?

DOCK10 p.Gly173Val (c.518G>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about DOCK10 p.Gly173Val (c.518G>T)?

AlphaMissense predicts ambiguous (score 0.4001) — an in-silico prediction, not a clinical call.

DOCK10 p.Gly173Val

c.518G>T · VCV4661662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4001 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
AlphaMissense	0.4001	ambiguous
REVEL	0.349	indeterminate
SaProt	LLR -7.36	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 219 kb · p 0.24 · regional, not allelic
Overall
CADD	26.3	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 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00198% 32/1,613,730 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
African / African-American	0.00401%	24,961
South Asian	0.00329%	30,357
Finnishnot grpmax-eligible	0.00312%	32,002
European (non-Finnish)	0.00178%	56,184
Admixed American	0.00167%	59,980
Remaining individualsnot grpmax-eligible	0.0016%	62,454

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.Gly173Val
Coding: c.518G>T
MANE Select: NM_014689
Type: single nucleotide variant
Location: chr2:224886157 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.47 · 4 PDB
Residue 173: the 'disordered' region

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

Similar variants

DOCK10 p.Gly173Ala Uncertain significance ★ ⚠ same residue
DOCK10 p.Gly173Glu Uncertain significance ★ ⚠ same residue
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

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-gly173val (accessed [today's date]).

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