Is DOCK5 p.Phe551= (c.1653C>T) pathogenic?

DOCK5 p.Phe551= (c.1653C>T) is classified Likely benign in DOCK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). Ultra-rare (popmax 0.0413%, nfe).

How common is DOCK5 p.Phe551= (c.1653C>T) in the general population?

DOCK5 p.Phe551= (c.1653C>T) is ultra-rare (popmax 0.0413%, nfe) (gnomAD).

DOCK5 p.Phe551=

c.1653C>T · rs146969490 · VCV2658491

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0413%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.139	moderately benign-leaning
Splicing
SpliceAI	Δ0.26	acceptor loss, 37 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -1.3	GERP -3.5
Overall
CADD	6.659	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0413% European (non-Finnish) · 487/1,179,734 alleles

Filtering AF 0.0382% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.037%

Overall 0.0562% 906/1,613,490 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.442%	226
Ashkenazi Jewishnot grpmax-eligible	0.372%	269
European (non-Finnish)grpmax	0.0413%	2,422
Remaining individualsnot grpmax-eligible	0.0352%	2,840
African / African-American	0.004%	25,003
South Asian	0.0011%	90,926

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe551=
Coding: c.1653C>T
MANE Select: NM_024940
dbSNP: rs146969490
Type: single nucleotide variant
Location: chr8:25323885 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.63 · 11 PDB
Residue 551: the c2 dock-type domain

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

Similar variants

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
DOCK5 p.Ala1194Ser 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-phe551 (accessed [today's date]).

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