Is DOCK4 p.Arg127Gln (c.380G>A) pathogenic?

DOCK4 p.Arg127Gln (c.380G>A) is classified Uncertain significance in DOCK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-30). AlphaMissense: likely benign (0.2185); Very rare (popmax 0.00659%, sas).

How common is DOCK4 p.Arg127Gln (c.380G>A) in the general population?

DOCK4 p.Arg127Gln (c.380G>A) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about DOCK4 p.Arg127Gln (c.380G>A)?

AlphaMissense predicts likely benign (score 0.2185) — an in-silico prediction, not a clinical call.

DOCK4 p.Arg127Gln

c.380G>A · rs540082296 · VCV2603848

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2185 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2185	likely benign
REVEL	0.268	benign-leaning
SaProt	LLR -5.49	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 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 465 kb · p 2.8e-18 · regional, not allelic
Overall
CADD	31.0	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,080 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000558% 9/1,614,014 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,180
Admixed American	0.00167%	60,036
European (non-Finnish)	0.00017%	589,950

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.Arg127Gln
Coding: c.380G>A
MANE Select: NM_001363540
dbSNP: rs540082296
Type: single nucleotide variant
Location: chr7:111989099 (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.Arg127Trp Uncertain significance ★ ⚠ same residue
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

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-arg127gln (accessed [today's date]).

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