Is SMARCA4 p.Ser224= (c.672G>T) pathogenic?

SMARCA4 p.Ser224= (c.672G>T) is classified Conflicting classifications of pathogenicity in SMARCA4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-15). No allele count reported in gnomAD v4.1 (AN 1,546,448); Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCA4 p.Ser224= (c.672G>T)?

SMARCA4 p.Ser224= (c.672G>T) is associated with hereditary neoplastic syndrome, rhabdoid tumor predisposition syndrome 2 (ClinVar).

How common is SMARCA4 p.Ser224= (c.672G>T) in the general population?

SMARCA4 p.Ser224= (c.672G>T) is no allele count reported in gnomAD v4.1 (AN 1,546,448) (gnomAD).

SMARCA4 p.Ser224=

c.672G>T · rs775288964 · VCV1124153

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,546,448)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.47	acceptor gain · deltas
Pangolin	Δ0.35	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -4.6	GERP -3.7
Overall
CADD	7.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,546,448). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SMARCA4
Protein: p.Ser224=
Coding: c.672G>T
MANE Select: NM_003072
dbSNP: rs775288964
Type: single nucleotide variant
Location: chr19:10986505 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 224: 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.Ser224Leu Uncertain significance ★★ ⚠ same residue
SMARCA4 p.Ser224fs Pathogenic ★ 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
SMARCA4 c.3546+1G>A 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-ser224 (accessed [today's date]).

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