Is SMARCB1 p.Ser148= (c.444C>T) pathogenic?

SMARCB1 p.Ser148= (c.444C>T) is classified Conflicting classifications of pathogenicity in SMARCB1 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-02-02). Rare (popmax 0.362%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCB1 p.Ser148= (c.444C>T)?

SMARCB1 p.Ser148= (c.444C>T) is associated with hereditary neoplastic syndrome, SMARCB1-related schwannomatosis (ClinVar).

How common is SMARCB1 p.Ser148= (c.444C>T) in the general population?

SMARCB1 p.Ser148= (c.444C>T) is rare (popmax 0.362%, afr) (gnomAD).

SMARCB1 p.Ser148=

c.444C>T · rs138184483 · VCV416324

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.362%, afr)

Conditions

hereditary neoplastic syndrome

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 -0.2	GERP -2.1, phastCons 0.25
Overall
CADD	8.177	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.362% African / African-American · 272/75,046 alleles

Filtering AF 0.327% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.313%

Overall 0.0203% 327/1,614,136 alleles · rare exomes 165/1,461,818 · genomes 162/152,318 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.362%	276
Middle Eastern	0.099%	1,010
Admixed American	0.0367%	2,728
Remaining individualsnot grpmax-eligible	0.032%	3,125
South Asian	0.00549%	18,217
European (non-Finnish)	0.000169%	589,981

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: SMARCB1
Protein: p.Ser148=
Coding: c.444C>T
MANE Select: NM_003073
dbSNP: rs138184483
Type: single nucleotide variant
Location: chr22:23801025 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.77 · 17 PDB
Residue 148: an α-helix

Full SMARCB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: SMARCB1-related schwannomatosis

Similar variants

SMARCB1 c.795+1G>A Likely pathogenic ★★ same condition
SMARCB1 c.93+1G>A Likely pathogenic ★★ same condition
SMARCB1 c.986+1G>A Likely pathogenic ★★ same condition
SMARCB1 c.*82C>T Pathogenic/Likely pathogenic ★★ same condition
SMARCB1 p.Arg158Ter Pathogenic ★★ same condition
SMARCB1 p.Arg201Ter Pathogenic ★★ same condition
SMARCB1 p.Arg374Gln Pathogenic/Likely pathogenic ★★ same condition
SMARCB1 p.Arg377His 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/smarcb1-p-ser148 (accessed [today's date]).

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