Is SBK3 p.Phe84Val (c.250T>G) pathogenic?

SBK3 p.Phe84Val (c.250T>G) is classified Uncertain significance in SBK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). AlphaMissense: likely pathogenic (0.8468); Rare (popmax 0.101%, sas).

How common is SBK3 p.Phe84Val (c.250T>G) in the general population?

SBK3 p.Phe84Val (c.250T>G) is rare (popmax 0.101%, sas) (gnomAD).

What do computational predictors say about SBK3 p.Phe84Val (c.250T>G)?

AlphaMissense predicts likely pathogenic (score 0.8468) — an in-silico prediction, not a clinical call.

SBK3 p.Phe84Val

c.250T>G · VCV3316268

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8468 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.101%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8468	likely pathogenic
REVEL	0.21	benign-leaning
SaProt	LLR -10.58	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.89, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 4,694 bp · p 0.37 · regional, not allelic
Overall
CADD	25.3	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 0.101% South Asian · 85/84,070 alleles

Filtering AF 0.0837% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0773%

Overall 0.00579% 89/1,535,990 alleles · rare exomes 86/1,383,750 · genomes 3/152,240 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.101%	989
Remaining individualsnot grpmax-eligible	0.00333%	30,005
East Asian	0.00244%	40,912
European (non-Finnish)	8.72e-05%	1,146,864

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: SBK3
Protein: p.Phe84Val
Coding: c.250T>G
MANE Select: NM_001199824
Type: single nucleotide variant
Location: chr19:55544249 (GRCh38)
Gene constraint: LOEUF 1.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.35
Residue 84: the protein kinase domain

Full SBK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SBK3 p.Ala117Thr Uncertain significance ★ ⚠ same type
SBK3 p.Ala121Val Uncertain significance ★ ⚠ same type
SBK3 p.Ala196Thr Uncertain significance ★ ⚠ same type
SBK3 p.Ala256Thr Uncertain significance ★ ⚠ same type
SBK3 p.Ala60Thr Uncertain significance ★ ⚠ same type
SBK3 p.Arg112Gly Uncertain significance ★ ⚠ same type
SBK3 p.Arg142Gln Uncertain significance ★ ⚠ same type
SBK3 p.Arg178His 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/sbk3-p-phe84val (accessed [today's date]).

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