Is DOK4 p.Asp95Ala (c.284A>C) pathogenic?

DOK4 p.Asp95Ala (c.284A>C) is classified Uncertain significance in DOK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). AlphaMissense: likely pathogenic (0.5741); Absent from gnomAD v4.1.

How common is DOK4 p.Asp95Ala (c.284A>C) in the general population?

DOK4 p.Asp95Ala (c.284A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOK4 p.Asp95Ala (c.284A>C)?

AlphaMissense predicts likely pathogenic (score 0.5741) — an in-silico prediction, not a clinical call.

DOK4 p.Asp95Ala

c.284A>C · rs1719861399 · VCV2333948

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5741 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.5741	likely pathogenic
REVEL	0.5	indeterminate
SaProt	LLR -11.59	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 6,127 bp · p 0.03 · regional, not allelic
Overall
CADD	27.7	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: DOK4
Protein: p.Asp95Ala
Coding: c.284A>C
MANE Select: NM_018110
dbSNP: rs1719861399
Type: single nucleotide variant
Location: chr16:57475511 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 95: the ph domain

Full DOK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOK4 p.Asp95Asn Uncertain significance ★ same residue
DOK4 p.Glu74Asp Benign ★★ same type
DOK4 p.Ala191Thr Uncertain significance ★ ⚠ same type
DOK4 p.Ala204Thr Uncertain significance ★ ⚠ same type
DOK4 p.Ala229Ser Uncertain significance ★ ⚠ same type
DOK4 p.Ala294Gly Uncertain significance ★ ⚠ same type
DOK4 p.Ala294Pro Uncertain significance ★ ⚠ same type
DOK4 p.Arg115Cys Uncertain significance ★ ⚠ 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/dok4-p-asp95ala (accessed [today's date]).

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