Is BRSK2 p.Phe335= (c.1005C>T) pathogenic?

BRSK2 p.Phe335= (c.1005C>T) is classified Likely benign in BRSK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). Rare (popmax 0.105%, afr); Associated with Inborn genetic diseases.

What condition is associated with BRSK2 p.Phe335= (c.1005C>T)?

BRSK2 p.Phe335= (c.1005C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BRSK2 p.Phe335= (c.1005C>T) in the general population?

BRSK2 p.Phe335= (c.1005C>T) is rare (popmax 0.105%, afr) (gnomAD).

BRSK2 p.Phe335=

c.1005C>T · VCV3825750

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.105%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.3	phastCons 0.17
Overall
CADD	9.456	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% African / African-American · 78/74,074 alleles

Filtering AF 0.0865% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0795%

Overall 0.00547% 86/1,573,308 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.105%	950
East Asian	0.00705%	14,179
Admixed American	0.00189%	53,016
Remaining individualsnot grpmax-eligible	0.00164%	60,888
South Asian	0.00115%	87,208
European (non-Finnish)	0.000172%	579,838

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: BRSK2
Protein: p.Phe335=
Coding: c.1005C>T
MANE Select: NM_001256627
Type: single nucleotide variant
Location: chr11:1445598 (GRCh38)
Gene constraint: LOEUF 0.361 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.46
Residue 335: the uba domain

Full BRSK2 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

BRSK2 p.Arg65Gln Uncertain significance ★★ ⚠ same condition
BRSK2 p.Asp7Asn Uncertain significance ★★ ⚠ same condition
BRSK2 p.Gly391Ser Likely benign ★★ ⚠ same condition
BRSK2 p.Gly578Ala Benign/Likely benign ★★ same condition
BRSK2 p.Pro502Leu Likely benign ★★ same condition
BRSK2 c.1226+1G>A Likely pathogenic ★ same condition
BRSK2 c.978-1G>C Pathogenic ★ same condition
BRSK2 p.Pro184His Likely pathogenic ★ 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/brsk2-p-phe335 (accessed [today's date]).

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