Is DOCK7 p.Ala1154Val (c.3461C>T) pathogenic?

DOCK7 p.Ala1154Val (c.3461C>T) is classified Uncertain significance in DOCK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). AlphaMissense: ambiguous (0.4776); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with DOCK7 p.Ala1154Val (c.3461C>T)?

DOCK7 p.Ala1154Val (c.3461C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK7 p.Ala1154Val (c.3461C>T) in the general population?

DOCK7 p.Ala1154Val (c.3461C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about DOCK7 p.Ala1154Val (c.3461C>T)?

AlphaMissense predicts ambiguous (score 0.4776) — an in-silico prediction, not a clinical call.

DOCK7 p.Ala1154Val

c.3461C>T · VCV4014240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4776 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4776	ambiguous
REVEL	0.18	moderately benign-leaning
SaProt	LLR -5.04	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.24	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 175 kb · p 3.6e-10 · regional, not allelic
Overall
CADD	25.2	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 0.00134% African / African-American · 1/74,896 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000744% 12/1,613,122 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,896
European (non-Finnish)	0.000933%	107,219

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: DOCK7
Protein: p.Ala1154Val
Coding: c.3461C>T
MANE Select: NM_001367561
Type: single nucleotide variant
Location: chr1:62537901 (GRCh38)
Gene constraint: LOEUF 0.551 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 2 PDB

Full DOCK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK7 p.Ala1154Pro Uncertain significance ★ ⚠ same residue
DOCK7 c.3781+4C>G Uncertain significance ★★ same condition
DOCK7 p.Ala1479Thr Uncertain significance ★★ ⚠ same condition
DOCK7 p.Ala205Thr Uncertain significance ★★ ⚠ same condition
DOCK7 p.Arg1266Gln Uncertain significance ★★ ⚠ same condition
DOCK7 p.Arg1358Gln Uncertain significance ★★ ⚠ same condition
DOCK7 p.Arg1380Gln Uncertain significance ★★ ⚠ same condition
DOCK7 p.Arg1634Gly Uncertain significance ★★ ⚠ same condition

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/dock7-p-ala1154val (accessed [today's date]).

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