Is DOCK4 p.Arg1579Lys (c.4736G>A) pathogenic?

DOCK4 p.Arg1579Lys (c.4736G>A) is classified Benign in DOCK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-26). AlphaMissense: likely benign (0.121); Low-frequency (popmax 1.14%, eas).

How common is DOCK4 p.Arg1579Lys (c.4736G>A) in the general population?

DOCK4 p.Arg1579Lys (c.4736G>A) is low-frequency (popmax 1.14%, eas) (gnomAD).

What do computational predictors say about DOCK4 p.Arg1579Lys (c.4736G>A)?

AlphaMissense predicts likely benign (score 0.121) — an in-silico prediction, not a clinical call.

DOCK4 p.Arg1579Lys

c.4736G>A · rs3757650 · VCV732238

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.121 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.14%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.121	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -3.41	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 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 465 kb · p 2.8e-18 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R1570K vs ClinVar R1579K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.14% East Asian · 512/44,730 alleles

Filtering AF 1.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.03%

Overall 0.0342% 550/1,608,566 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.14%	87
Remaining individualsnot grpmax-eligible	0.053%	1,888
Middle Eastern	0.0166%	6,036
South Asian	0.00111%	89,902
European (non-Finnish)	0.000255%	392,639

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.Arg1579Lys
Coding: c.4736G>A
MANE Select: NM_001363540
dbSNP: rs3757650
Type: single nucleotide variant
Location: chr7:111742074 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.47
Residue 1579: the docker domain

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-arg1579lys (accessed [today's date]).

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