Is DOCK4 p.Pro1739Ala (c.5215C>G) pathogenic?

DOCK4 p.Pro1739Ala (c.5215C>G) is classified Uncertain significance in DOCK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely benign (0.0495); Very rare (popmax 0.00932%, nfe).

How common is DOCK4 p.Pro1739Ala (c.5215C>G) in the general population?

DOCK4 p.Pro1739Ala (c.5215C>G) is very rare (popmax 0.00932%, nfe) (gnomAD).

What do computational predictors say about DOCK4 p.Pro1739Ala (c.5215C>G)?

AlphaMissense predicts likely benign (score 0.0495) — an in-silico prediction, not a clinical call.

DOCK4 p.Pro1739Ala

c.5215C>G · VCV4243920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0495 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00932%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0495	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -6.82	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 8.5	GERP 0.77, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 13 kb · p 0.00031 · regional, not allelic
Overall
CADD	21.9	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 P1730A vs ClinVar P1739A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00932% European (non-Finnish) · 110/1,179,658 alleles

Filtering AF 0.00791% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00736%

Overall 0.00773% 113/1,461,446 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00932%	10,724
Remaining individualsnot grpmax-eligible	0.0032%	31,239
African / African-American	0.00133%	75,044

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: DOCK4
Protein: p.Pro1739Ala
Coding: c.5215C>G
MANE Select: NM_001363540
Type: single nucleotide variant
Location: chr7:111739151 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.47

Full DOCK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK4 p.Arg490Trp Uncertain significance ★★ ⚠ same type
DOCK4 p.Gln1223Arg Uncertain significance ★★ ⚠ same type
DOCK4 p.His1716Tyr Uncertain significance ★★ ⚠ same type
DOCK4 p.Pro1641Leu Uncertain significance ★★ ⚠ same type
DOCK4 p.Ser750Arg Uncertain significance ★★ ⚠ same type
DOCK4 c.550-8T>C Benign/Likely benign ★★ same type
DOCK4 p.Arg106Cys Benign/Likely benign ★★ ⚠ same type
DOCK4 p.Arg106His Benign/Likely benign ★★ 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/dock4-p-pro1739ala (accessed [today's date]).

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