Is DOK7 p.Ile80Phe (c.238A>T) pathogenic?

DOK7 p.Ile80Phe (c.238A>T) is classified Uncertain significance in DOK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: likely pathogenic (0.6212); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DOK7 p.Ile80Phe (c.238A>T)?

DOK7 p.Ile80Phe (c.238A>T) is associated with Inborn genetic diseases (ClinVar).

How common is DOK7 p.Ile80Phe (c.238A>T) in the general population?

DOK7 p.Ile80Phe (c.238A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOK7 p.Ile80Phe (c.238A>T)?

AlphaMissense predicts likely pathogenic (score 0.6212) — an in-silico prediction, not a clinical call.

DOK7 p.Ile80Phe

c.238A>T · VCV3504681

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6212 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6212	likely pathogenic
REVEL	0.774	moderately pathogenic-leaning
SaProt	LLR -12.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP 0.97, phastCons 1
Regional constraint	o/e 1.44	unconstrained · MANE · 30 kb · p 2.5e-31 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DOK7
Protein: p.Ile80Phe
Coding: c.238A>T
MANE Select: NM_173660
Type: single nucleotide variant
Location: chr4:3473543 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 80: the ph domain

Full DOK7 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

DOK7 p.Ala251Val Uncertain significance ★★ ⚠ same condition
DOK7 p.Ala356Val Uncertain significance ★★ ⚠ same condition
DOK7 p.Ala380Val Uncertain significance ★★ ⚠ same condition
DOK7 p.Ala403Gly Uncertain significance ★★ ⚠ same condition
DOK7 p.Ala482Glu Uncertain significance ★★ ⚠ same condition
DOK7 p.Ala482Val Uncertain significance ★★ ⚠ same condition
DOK7 p.Arg105His Uncertain significance ★★ ⚠ same condition
DOK7 p.Arg244Trp 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/dok7-p-ile80phe (accessed [today's date]).

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