Is DOCK1 p.Val1350Ile (c.4048G>A) pathogenic?

DOCK1 p.Val1350Ile (c.4048G>A) is classified Uncertain significance in DOCK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-12). AlphaMissense: likely benign (0.0954); Very rare (popmax 0.00509%, nfe).

How common is DOCK1 p.Val1350Ile (c.4048G>A) in the general population?

DOCK1 p.Val1350Ile (c.4048G>A) is very rare (popmax 0.00509%, nfe) (gnomAD).

What do computational predictors say about DOCK1 p.Val1350Ile (c.4048G>A)?

AlphaMissense predicts likely benign (score 0.0954) — an in-silico prediction, not a clinical call.

DOCK1 p.Val1350Ile

c.4048G>A · rs748476214 · VCV2306740

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0954 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00509%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0954	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -1.22	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 8.5	phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 41 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	23.4	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V1329I vs ClinVar V1350I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00509% European (non-Finnish) · 60/1,179,794 alleles

Filtering AF 0.00402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00362%

Overall 0.00409% 66/1,613,596 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00509%	19,663
Remaining individualsnot grpmax-eligible	0.0032%	31,230
African / African-American	0.00267%	37,448
Admixed American	0.00167%	59,994
Finnishnot grpmax-eligible	0.00156%	64,000

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: DOCK1
Protein: p.Val1350Ile
Coding: c.4048G>A
MANE Select: NM_001290223
dbSNP: rs748476214
Type: single nucleotide variant
Location: chr10:127404355 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.63 · 1 PDB
Residue 1350: the docker domain

Full DOCK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK1 p.Pro1783Ser Uncertain significance ★★ ⚠ same type
DOCK1 p.Ala1185Thr Uncertain significance ★ ⚠ same type
DOCK1 p.Ala151Thr Uncertain significance ★ ⚠ same type
DOCK1 p.Ala1578Ser Uncertain significance ★ ⚠ same type
DOCK1 p.Ala1590Gly Uncertain significance ★ ⚠ same type
DOCK1 p.Ala1620Val Uncertain significance ★ ⚠ same type
DOCK1 p.Ala1689Ser Uncertain significance ★ ⚠ same type
DOCK1 p.Ala280Thr 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/dock1-p-val1350ile (accessed [today's date]).

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