Is DOCK6 p.Trp1353Ter (c.4058G>A) pathogenic?

DOCK6 p.Trp1353Ter (c.4058G>A) is classified Pathogenic in DOCK6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). Ultra-rare (popmax 0.022%, sas).

How common is DOCK6 p.Trp1353Ter (c.4058G>A) in the general population?

DOCK6 p.Trp1353Ter (c.4058G>A) is ultra-rare (popmax 0.022%, sas) (gnomAD).

DOCK6 p.Trp1353Ter

c.4058G>A · VCV3700877

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 32 of 48
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Overall
CADD	47.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.022% South Asian · 20/91,076 alleles

Filtering AF 0.0145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00136% 22/1,613,614 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.022%	4,554
Remaining individualsnot grpmax-eligible	0.0016%	62,456
European (non-Finnish)	8.48e-05%	1,179,878

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: DOCK6
Protein: p.Trp1353Ter
Coding: c.4058G>A
MANE Select: NM_020812
Type: single nucleotide variant
Location: chr19:11215435 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB

Full DOCK6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK6 c.4491+1G>A Pathogenic ★★ same type
DOCK6 c.5939+2T>C Pathogenic ★★ same type
DOCK6 c.807-1G>A Likely pathogenic ★★ same type
DOCK6 p.Arg1526Ter Pathogenic/Likely pathogenic ★★ same type
DOCK6 p.Arg184Ter Pathogenic/Likely pathogenic ★★ same type
DOCK6 p.Arg488Ter Pathogenic/Likely pathogenic ★★ same type
DOCK6 p.Gln1188Ter Pathogenic/Likely pathogenic ★★ same type
DOCK6 p.Glu1494Ter 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/dock6-p-trp1353ter (accessed [today's date]).

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