Is SMARCA4 p.Lys348= (c.1044G>A) pathogenic?

SMARCA4 p.Lys348= (c.1044G>A) is classified Benign/Likely benign in SMARCA4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0169%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCA4 p.Lys348= (c.1044G>A)?

SMARCA4 p.Lys348= (c.1044G>A) is associated with hereditary neoplastic syndrome, rhabdoid tumor predisposition syndrome 2 (ClinVar).

How common is SMARCA4 p.Lys348= (c.1044G>A) in the general population?

SMARCA4 p.Lys348= (c.1044G>A) is ultra-rare (popmax 0.0169%, mid) (gnomAD).

SMARCA4 p.Lys348=

c.1044G>A · rs566093923 · VCV391823

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, mid)

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 6.5	GERP 2.2, phastCons 1
Overall
CADD	10.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0169% Middle Eastern · 1/5,904 alleles

Filtering AF 0.00503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00463%

Overall 0.00571% 92/1,612,170 alleles · ultra-rare exomes 86/1,459,852 · genomes 6/152,318 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0169%	5,904
Remaining individualsnot grpmax-eligible	0.0144%	6,931
Admixed American	0.01%	9,987
Ashkenazi Jewishnot grpmax-eligible	0.00677%	14,776
European (non-Finnish)	0.00619%	16,159
East Asian	0.00223%	44,860

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: SMARCA4
Protein: p.Lys348=
Coding: c.1044G>A
MANE Select: NM_003072
dbSNP: rs566093923
Type: single nucleotide variant
Location: chr19:10987850 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 348: 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 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
SMARCA4 c.3774+2T>A Likely pathogenic ★★ same condition
SMARCA4 c.3951+2T>C 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-lys348 (accessed [today's date]).

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