Is DOCK11 p.Ile72Val (c.214A>G) pathogenic?

DOCK11 p.Ile72Val (c.214A>G) is classified Uncertain significance in DOCK11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-28). AlphaMissense: likely benign (0.0678); Very rare (popmax 0.000338%, nfe).

How common is DOCK11 p.Ile72Val (c.214A>G) in the general population?

DOCK11 p.Ile72Val (c.214A>G) is very rare (popmax 0.000338%, nfe) (gnomAD).

What do computational predictors say about DOCK11 p.Ile72Val (c.214A>G)?

AlphaMissense predicts likely benign (score 0.0678) — an in-silico prediction, not a clinical call.

DOCK11 p.Ile72Val

c.214A>G · VCV3841916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0678 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000338%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0678	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -6.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.30	donor gain · deltas
Constraint at this position
Conservation	phyloP 2.9	GERP 0.74, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 190 kb · p 2e-21 · regional, not allelic
Overall
CADD	16.66	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 0.000338% European (non-Finnish) · 3/888,206 alleles

Filtering AF 9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000275% 3/1,089,896 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: DOCK11
Protein: p.Ile72Val
Coding: c.214A>G
MANE Select: NM_144658
Type: single nucleotide variant
Location: chrX:118542836 (GRCh38)
Structure: AlphaFold pLDDT 79.65

Full DOCK11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK11 p.Ala1222Val Uncertain significance ★★ ⚠ same type
DOCK11 p.Ala1665Val Uncertain significance ★★ ⚠ same type
DOCK11 p.Leu781His Uncertain significance ★★ ⚠ same type
DOCK11 p.Gln866Arg Benign ★★ same type
DOCK11 p.Ser842Leu Likely benign ★★ same type
DOCK11 c.1718+5G>A Pathogenic ★ same type
DOCK11 c.392+1G>A Likely pathogenic ★ same type
DOCK11 c.4582-1G>A Likely pathogenic ★ 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/dock11-p-ile72val (accessed [today's date]).

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