Is SMARCB1 p.Pro48Ser (c.142C>T) pathogenic?

SMARCB1 p.Pro48Ser (c.142C>T) is classified Uncertain significance in SMARCB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-08). AlphaMissense: likely pathogenic (0.9976); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCB1 p.Pro48Ser (c.142C>T)?

SMARCB1 p.Pro48Ser (c.142C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SMARCB1 p.Pro48Ser (c.142C>T) in the general population?

SMARCB1 p.Pro48Ser (c.142C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMARCB1 p.Pro48Ser (c.142C>T)?

AlphaMissense predicts likely pathogenic (score 0.9976) — an in-silico prediction, not a clinical call.

SMARCB1 p.Pro48Ser

c.142C>T · rs2517660395 · VCV1772465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9976 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9976	likely pathogenic
REVEL	0.83	moderately pathogenic-leaning
SaProt	LLR -12.56	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SMARCB1
Protein: p.Pro48Ser
Coding: c.142C>T
MANE Select: NM_003073
dbSNP: rs2517660395
Type: single nucleotide variant
Location: chr22:23791804 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.77 · 17 PDB
Residue 48: the 'dna-binding' region

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

Similar variants

SMARCB1 p.Pro48= Likely benign ★★ same residue
SMARCB1 p.Pro48Leu Uncertain significance ★ ⚠ same residue
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

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-pro48ser (accessed [today's date]).

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