Is DOCK10 p.Arg301Lys (c.902G>A) pathogenic?

DOCK10 p.Arg301Lys (c.902G>A) is classified Conflicting classifications of pathogenicity in DOCK10 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-13). AlphaMissense: likely benign (0.0658); Rare (popmax 0.99%, mid).

How common is DOCK10 p.Arg301Lys (c.902G>A) in the general population?

DOCK10 p.Arg301Lys (c.902G>A) is rare (popmax 0.99%, mid) (gnomAD).

What do computational predictors say about DOCK10 p.Arg301Lys (c.902G>A)?

AlphaMissense predicts likely benign (score 0.0658) — an in-silico prediction, not a clinical call.

DOCK10 p.Arg301Lys

c.902G>A · rs180691490 · VCV2651950

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0658 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.99%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0658	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -5.82	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 2.2	GERP 0.12, phastCons 0.98
Regional constraint	o/e 0.97	unconstrained · MANE · 219 kb · p 0.24 · regional, not allelic
Overall
CADD	14.83	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 0.99% Middle Eastern · 60/6,060 alleles

Filtering AF 0.79% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.717%

Overall 0.205% 3,311/1,613,786 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.99%	101
Ashkenazi Jewishnot grpmax-eligible	0.389%	257
Admixed American	0.305%	328
Remaining individualsnot grpmax-eligible	0.264%	379
European (non-Finnish)	0.216%	464
African / African-American	0.205%	487
South Asian	0.0791%	1,265
Finnishnot grpmax-eligible	0.0281%	3,557

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.Arg301Lys
Coding: c.902G>A
MANE Select: NM_014689
dbSNP: rs180691490
Type: single nucleotide variant
Location: chr2:224876067 (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-arg301lys (accessed [today's date]).

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