Is DOCK11 p.Val40Phe (c.118G>T) pathogenic?

DOCK11 p.Val40Phe (c.118G>T) is classified Uncertain significance in DOCK11 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: likely pathogenic (0.6108); Very rare (popmax 0.0022%, amr).

How common is DOCK11 p.Val40Phe (c.118G>T) in the general population?

DOCK11 p.Val40Phe (c.118G>T) is very rare (popmax 0.0022%, amr) (gnomAD).

What do computational predictors say about DOCK11 p.Val40Phe (c.118G>T)?

AlphaMissense predicts likely pathogenic (score 0.6108) — an in-silico prediction, not a clinical call.

DOCK11 p.Val40Phe

c.118G>T · rs140943491 · VCV2237042

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6108 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6108	likely pathogenic
REVEL	0.12	moderately benign-leaning
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -0.43, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 190 kb · p 2e-21 · regional, not allelic
Overall
CADD	23.5	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 0.0022% Admixed American · 1/45,403 alleles

Filtering AF 0.000164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000119%

Overall 0.000497% 6/1,206,189 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0022%	45,403
European (non-Finnish)	0.00056%	178,611

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.Val40Phe
Coding: c.118G>T
MANE Select: NM_144658
dbSNP: rs140943491
Type: single nucleotide variant
Location: chrX:118542740 (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-val40phe (accessed [today's date]).

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