Is DOK3 p.Pro436Arg (c.1307C>G) pathogenic?

DOK3 p.Pro436Arg (c.1307C>G) is classified Uncertain significance in DOK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-26). AlphaMissense: likely benign (0.1226); Rare (popmax 0.119%, mid).

How common is DOK3 p.Pro436Arg (c.1307C>G) in the general population?

DOK3 p.Pro436Arg (c.1307C>G) is rare (popmax 0.119%, mid) (gnomAD).

What do computational predictors say about DOK3 p.Pro436Arg (c.1307C>G)?

AlphaMissense predicts likely benign (score 0.1226) — an in-silico prediction, not a clinical call.

DOK3 p.Pro436Arg

c.1307C>G · rs754987743 · VCV3085179

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1226 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.119%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1226	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 0.13, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 5,554 bp · p 0.73 · regional, not allelic
Overall
CADD	23.1	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 P492R vs ClinVar P436R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.119% Middle Eastern · 6/5,054 alleles

Filtering AF 0.0517% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0353%

Overall 0.0154% 239/1,554,622 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.119%	842
Admixed American	0.0481%	2,078
Remaining individualsnot grpmax-eligible	0.0349%	2,867
European (non-Finnish)	0.0159%	6,284
South Asian	0.00353%	28,307
African / African-American	0.00136%	73,464

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: DOK3
Protein: p.Pro436Arg
Coding: c.1307C>G
MANE Select: NM_001308236
dbSNP: rs754987743
Type: single nucleotide variant
Location: chr5:177503999 (GRCh38)
Gene constraint: LOEUF 1.47 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.94
Residue 436: the 'disordered' region

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

Similar variants

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
DOK3 c.-62C>T Uncertain significance ★ ⚠ same type
DOK3 c.-69G>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-pro436arg (accessed [today's date]).

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