Is DOCK5 p.Arg211Trp (c.631C>T) pathogenic?

DOCK5 p.Arg211Trp (c.631C>T) is classified Uncertain significance in DOCK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). AlphaMissense: likely benign (0.1184); Ultra-rare (popmax 0.0692%, eas).

How common is DOCK5 p.Arg211Trp (c.631C>T) in the general population?

DOCK5 p.Arg211Trp (c.631C>T) is ultra-rare (popmax 0.0692%, eas) (gnomAD).

What do computational predictors say about DOCK5 p.Arg211Trp (c.631C>T)?

AlphaMissense predicts likely benign (score 0.1184) — an in-silico prediction, not a clinical call.

DOCK5 p.Arg211Trp

c.631C>T · VCV3841968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1184 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0692%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1184	likely benign
REVEL	0.258	benign-leaning
SaProt	LLR -12.56	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.3	GERP -2.9, phastCons 0.85
Regional constraint	o/e 1.03	unconstrained · MANE · 116 kb · p 0.58 · regional, not allelic
Overall
CADD	20.2	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 0.0692% East Asian · 31/44,816 alleles

Filtering AF 0.0501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0435%

Overall 0.00385% 62/1,612,084 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0692%	1,446
European (non-Finnish)	0.00237%	42,116
Admixed American	0.00168%	59,642
Remaining individualsnot grpmax-eligible	0.0016%	62,412
South Asian	0.0011%	90,682

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: DOCK5
Protein: p.Arg211Trp
Coding: c.631C>T
MANE Select: NM_024940
Type: single nucleotide variant
Location: chr8:25298968 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.63 · 11 PDB

Full DOCK5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK5 p.Arg211Gln Uncertain significance ★ ⚠ same residue
DOCK5 c.4788+9C>T Benign ★★ same type
DOCK5 p.Leu986Phe Benign/Likely benign ★★ ⚠ same type
DOCK5 p.Met987Leu Benign ★★ same type
DOCK5 p.Pro1467= Benign ★★ same type
DOCK5 p.Ser1306= Benign ★★ same type
DOCK5 p.Thr469Met Benign/Likely benign ★★ ⚠ same type
DOCK5 p.Ala1067Val 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/dock5-p-arg211trp (accessed [today's date]).

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