Is DOCK4 p.Ile951Val (c.2851A>G) pathogenic?

DOCK4 p.Ile951Val (c.2851A>G) is classified Uncertain significance in DOCK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-09). AlphaMissense: likely benign (0.1083); Very rare (popmax 0.000848%, nfe).

How common is DOCK4 p.Ile951Val (c.2851A>G) in the general population?

DOCK4 p.Ile951Val (c.2851A>G) is very rare (popmax 0.000848%, nfe) (gnomAD).

What do computational predictors say about DOCK4 p.Ile951Val (c.2851A>G)?

AlphaMissense predicts likely benign (score 0.1083) — an in-silico prediction, not a clinical call.

DOCK4 p.Ile951Val

c.2851A>G · rs1259098398 · VCV2390422

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1083 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1083	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Pangolin	Δ0.22	gain · loss 0.06 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 465 kb · p 2.8e-18 · regional, not allelic
Overall
CADD	22.6	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 0.000848% European (non-Finnish) · 10/1,179,482 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.00062% 10/1,612,788 alleles · very rare

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: DOCK4
Protein: p.Ile951Val
Coding: c.2851A>G
MANE Select: NM_001363540
dbSNP: rs1259098398
Type: single nucleotide variant
Location: chr7:111822441 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.47

Full DOCK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK4 p.Arg490Trp Uncertain significance ★★ ⚠ same type
DOCK4 p.Gln1223Arg Uncertain significance ★★ ⚠ same type
DOCK4 p.His1716Tyr Uncertain significance ★★ ⚠ same type
DOCK4 p.Pro1641Leu Uncertain significance ★★ ⚠ same type
DOCK4 p.Ser750Arg Uncertain significance ★★ same type
DOCK4 c.550-8T>C Benign/Likely benign ★★ same type
DOCK4 p.Arg106Cys Benign/Likely benign ★★ same type
DOCK4 p.Arg106His Benign/Likely benign ★★ 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/dock4-p-ile951val (accessed [today's date]).

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