Is DOK3 p.Ala252Asp (c.755C>A) pathogenic?

DOK3 p.Ala252Asp (c.755C>A) is classified Uncertain significance in DOK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). AlphaMissense: likely benign (0.1515); Absent from gnomAD v4.1.

How common is DOK3 p.Ala252Asp (c.755C>A) in the general population?

DOK3 p.Ala252Asp (c.755C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOK3 p.Ala252Asp (c.755C>A)?

AlphaMissense predicts likely benign (score 0.1515) — an in-silico prediction, not a clinical call.

DOK3 p.Ala252Asp

c.755C>A · VCV3504646

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1515 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,594,476)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1515	likely benign
REVEL	0.384	indeterminate
SaProt	LLR -7.71	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP -0.66, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 5,554 bp · p 0.73 · regional, not allelic
Overall
CADD	17.95	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A308D vs ClinVar A252D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,594,476). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DOK3
Protein: p.Ala252Asp
Coding: c.755C>A
MANE Select: NM_001308236
Type: single nucleotide variant
Location: chr5:177504551 (GRCh38)
Gene constraint: LOEUF 1.47 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.94
Residue 252: the irs-type ptb domain

Full DOK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOK3 p.Ala252Pro Uncertain significance ★ ⚠ same residue
DOK3 p.Ala252Thr Likely benign ★ same residue
DOK3 c.-102G>T Uncertain significance ★ ⚠ same type
DOK3 c.-181C>T Uncertain significance ★ ⚠ same type
DOK3 c.-182G>A Uncertain significance ★ ⚠ same type
DOK3 c.-182G>C Uncertain significance ★ ⚠ same type
DOK3 c.-23C>T Uncertain significance ★ ⚠ same type
DOK3 c.-35G>A 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/dok3-p-ala252asp (accessed [today's date]).

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