Is DOK7 p.Met1del (c.-5AGA[1]) pathogenic?

DOK7 p.Met1del (c.-5AGA[1]) is classified Uncertain significance in DOK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-10). Very rare (popmax 0.000265%, nfe).

How common is DOK7 p.Met1del (c.-5AGA[1]) in the general population?

DOK7 p.Met1del (c.-5AGA[1]) is very rare (popmax 0.000265%, nfe) (gnomAD).

DOK7 p.Met1del

c.-5AGA[1] · VCV3336041

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000265%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 0.65, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000265% European (non-Finnish) · 3/1,132,840 alleles

Filtering AF 7.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000224% 3/1,337,576 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: DOK7
Protein: p.Met1del
Coding: c.-5AGA[1]
MANE Select: NM_173660
Type: Microsatellite
Location: chr4:3463371 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61

Full DOK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOK7 p.Asp417fs Pathogenic/Likely pathogenic ★★ same type
DOK7 p.Gly448fs Pathogenic ★★ same type
DOK7 p.Leu447fs Pathogenic/Likely pathogenic ★★ same type
DOK7 p.Leu389fs Likely pathogenic ★ same type
DOK7 p.Ser347fs Pathogenic ★ same type
DOK7 p.Ser291del Uncertain significance ★ same type
DOK7 c.331+11GGGGCC[3] Likely benign ★ same type
DOK7 c.331+20_331+25del 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/dok7-p-met1del (accessed [today's date]).

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