Is DOCK10 p.Ala1534Val (c.4601C>T) pathogenic?

DOCK10 p.Ala1534Val (c.4601C>T) is classified Uncertain significance in DOCK10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.2838); Ultra-rare (popmax 0.0223%, eas).

How common is DOCK10 p.Ala1534Val (c.4601C>T) in the general population?

DOCK10 p.Ala1534Val (c.4601C>T) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about DOCK10 p.Ala1534Val (c.4601C>T)?

AlphaMissense predicts likely benign (score 0.2838) — an in-silico prediction, not a clinical call.

DOCK10 p.Ala1534Val

c.4601C>T · VCV3273288

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2838 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2838	likely benign
REVEL	0.229	benign-leaning
SaProt	LLR -3.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 58 kb · p 1e-10 · regional, not allelic
Overall
CADD	26.2	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 0.0223% East Asian · 10/44,888 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.00663% 107/1,613,740 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,489
Remaining individualsnot grpmax-eligible	0.0128%	7,808
European (non-Finnish)	0.00712%	14,045
Admixed American	0.00333%	29,995
South Asian	0.0022%	45,541
African / African-American	0.00134%	74,906

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.Ala1534Val
Coding: c.4601C>T
MANE Select: NM_014689
Type: single nucleotide variant
Location: chr2:224797875 (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-ala1534val (accessed [today's date]).

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