Is DOCK6 p.Ser612Phe (c.1835C>T) pathogenic?

DOCK6 p.Ser612Phe (c.1835C>T) is classified Uncertain significance in DOCK6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.2248); Ultra-rare (popmax 0.0132%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DOCK6 p.Ser612Phe (c.1835C>T)?

DOCK6 p.Ser612Phe (c.1835C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK6 p.Ser612Phe (c.1835C>T) in the general population?

DOCK6 p.Ser612Phe (c.1835C>T) is ultra-rare (popmax 0.0132%, nfe) (gnomAD).

What do computational predictors say about DOCK6 p.Ser612Phe (c.1835C>T)?

AlphaMissense predicts likely benign (score 0.2248) — an in-silico prediction, not a clinical call.

DOCK6 p.Ser612Phe

c.1835C>T · rs368164863 · VCV2384092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2248 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2248	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -10.11	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 5.3	GERP 1.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	22.8	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 0.0132% European (non-Finnish) · 153/1,155,606 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00984% 154/1,565,416 alleles · ultra-rare exomes 149/1,413,350 · genomes 5/152,066 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0132%	7,553
African / African-American	0.00136%	73,680

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: DOCK6
Protein: p.Ser612Phe
Coding: c.1835C>T
MANE Select: NM_020812
dbSNP: rs368164863
Type: single nucleotide variant
Location: chr19:11237777 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB
Residue 612: the c2 dock-type domain

Full DOCK6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK6 c.5939+2T>C Pathogenic ★★ same condition
DOCK6 p.Glu1494Ter Pathogenic ★★ same condition
DOCK6 p.Ala1153Thr Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala1207Val Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala1241Thr Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala1319Val Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala133Thr Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala1481Thr Uncertain significance ★★ ⚠ same condition

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/dock6-p-ser612phe (accessed [today's date]).

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