Is SMARCA4 p.Ser38Phe (c.113C>T) pathogenic?

SMARCA4 p.Ser38Phe (c.113C>T) is classified Uncertain significance in SMARCA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-31). AlphaMissense: ambiguous (0.4666); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCA4 p.Ser38Phe (c.113C>T)?

SMARCA4 p.Ser38Phe (c.113C>T) is associated with hereditary neoplastic syndrome, rhabdoid tumor predisposition syndrome 2 (ClinVar).

How common is SMARCA4 p.Ser38Phe (c.113C>T) in the general population?

SMARCA4 p.Ser38Phe (c.113C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMARCA4 p.Ser38Phe (c.113C>T)?

AlphaMissense predicts ambiguous (score 0.4666) — an in-silico prediction, not a clinical call.

SMARCA4 p.Ser38Phe

c.113C>T · rs2145723650 · VCV2452860

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4666 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.4666	ambiguous
REVEL	0.516	indeterminate
SaProt	LLR -9.29	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 2,200 bp · p 0.0027 · regional, not allelic
Overall
CADD	24.3	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

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: SMARCA4
Protein: p.Ser38Phe
Coding: c.113C>T
MANE Select: NM_003072
dbSNP: rs2145723650
Type: single nucleotide variant
Location: chr19:10984264 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 38: the 'necessary for interaction with ss18l1/crest' region; the 'disordered' region

Full SMARCA4 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: rhabdoid tumor predisposition syndrome 2

Similar variants

SMARCA4 p.Ser38Pro Uncertain significance ★★ ⚠ same residue
SMARCA4 p.Ser38= Likely benign ★★ same residue
SMARCA4 p.Ser38Cys Uncertain significance ★ ⚠ same residue
SMARCA4 c.1943+1G>A Likely pathogenic ★★ same condition
SMARCA4 c.2274+1G>T Likely pathogenic ★★ same condition
SMARCA4 c.2438+1G>A Pathogenic/Likely pathogenic ★★ same condition
SMARCA4 c.3216-1G>C Likely pathogenic ★★ same condition
SMARCA4 c.3216-2A>G 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/smarca4-p-ser38phe (accessed [today's date]).

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