Is DOK5 p.Ala34Pro (c.100G>C) pathogenic?

DOK5 p.Ala34Pro (c.100G>C) is classified Uncertain significance in DOK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: likely pathogenic (0.568); Very rare (popmax 0.00695%, nfe).

How common is DOK5 p.Ala34Pro (c.100G>C) in the general population?

DOK5 p.Ala34Pro (c.100G>C) is very rare (popmax 0.00695%, nfe) (gnomAD).

What do computational predictors say about DOK5 p.Ala34Pro (c.100G>C)?

AlphaMissense predicts likely pathogenic (score 0.568) — an in-silico prediction, not a clinical call.

DOK5 p.Ala34Pro

c.100G>C · VCV3504666

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.568 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00695%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.568	likely pathogenic
REVEL	0.54	indeterminate
SaProt	LLR -9.31	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 175 kb · p 0.31 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00695% European (non-Finnish) · 82/1,179,786 alleles

Filtering AF 0.00571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00525%

Overall 0.00514% 83/1,613,710 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00695%	14,388
Remaining individualsnot grpmax-eligible	0.0016%	62,476

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: DOK5
Protein: p.Ala34Pro
Coding: c.100G>C
MANE Select: NM_018431
Type: single nucleotide variant
Location: chr20:54554966 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.32 · 1 PDB
Residue 34: the ph domain

Full DOK5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOK5 p.Ala34Thr Uncertain significance ★★ ⚠ same residue
DOK5 p.Arg185Gln Uncertain significance ★ ⚠ same type
DOK5 p.Arg186Gln Uncertain significance ★ ⚠ same type
DOK5 p.Arg186Trp Uncertain significance ★ ⚠ same type
DOK5 p.Arg236Leu Uncertain significance ★ ⚠ same type
DOK5 p.Arg253Trp Uncertain significance ★ ⚠ same type
DOK5 p.Asn117Ser Uncertain significance ★ ⚠ same type
DOK5 p.Asp87Asn 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/dok5-p-ala34pro (accessed [today's date]).

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