Is BRSK2 p.Val40= (c.120C>T) pathogenic?

BRSK2 p.Val40= (c.120C>T) is classified Likely benign in BRSK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). Very rare (popmax 0.00671%, amr).

How common is BRSK2 p.Val40= (c.120C>T) in the general population?

BRSK2 p.Val40= (c.120C>T) is very rare (popmax 0.00671%, amr) (gnomAD).

BRSK2 p.Val40=

c.120C>T · rs777512058 · VCV3067640

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00671%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3	phastCons 1
Overall
CADD	10.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00671% Admixed American · 4/59,570 alleles

Filtering AF 0.00227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00118% 19/1,608,704 alleles · very rare exomes 18/1,457,482 · genomes 1/151,222 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.019%	5,257
Admixed Americangrpmax	0.00671%	14,892
Remaining individualsnot grpmax-eligible	0.00161%	62,246
European (non-Finnish)	0.00017%	589,029

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: BRSK2
Protein: p.Val40=
Coding: c.120C>T
MANE Select: NM_001256627
dbSNP: rs777512058
Type: single nucleotide variant
Location: chr11:1436068 (GRCh38)
Gene constraint: LOEUF 0.361 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.46
Residue 40: the protein kinase domain

Full BRSK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRSK2 p.Arg313Ter Pathogenic/Likely pathogenic ★★ same type
BRSK2 p.Gly28Arg Likely pathogenic ★★ same type
BRSK2 p.Ala68Thr Uncertain significance ★★ ⚠ same type
BRSK2 p.Arg313Gln Uncertain significance ★★ same type
BRSK2 p.Arg65Gln Uncertain significance ★★ ⚠ same type
BRSK2 p.Asp7Asn Uncertain significance ★★ ⚠ same type
BRSK2 p.Leu70Pro Uncertain significance ★★ ⚠ same type
BRSK2 c.1288-6A>G Likely benign ★★ 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/brsk2-p-val40 (accessed [today's date]).

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