Is SMARCA2 p.Pro48Ser (c.142C>T) pathogenic?

SMARCA2 p.Pro48Ser (c.142C>T) is classified Likely benign in SMARCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-01). AlphaMissense: ambiguous (0.409); Very rare (popmax 0.00334%, amr); Associated with Inborn genetic diseases.

What condition is associated with SMARCA2 p.Pro48Ser (c.142C>T)?

SMARCA2 p.Pro48Ser (c.142C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SMARCA2 p.Pro48Ser (c.142C>T) in the general population?

SMARCA2 p.Pro48Ser (c.142C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about SMARCA2 p.Pro48Ser (c.142C>T)?

AlphaMissense predicts ambiguous (score 0.409) — an in-silico prediction, not a clinical call.

SMARCA2 p.Pro48Ser

c.142C>T · VCV4170122

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.409 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.409	ambiguous
REVEL	0.458	indeterminate
SaProt	LLR -9.73	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 11 kb · p 0.08 · regional, not allelic
Overall
CADD	25.4	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

Grpmax group 0.00334% Admixed American · 2/59,946 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,613,220 alleles · very rare exomes 2/1,460,856 · genomes 0/152,364 · joint denominator

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: SMARCA2
Protein: p.Pro48Ser
Coding: c.142C>T
MANE Select: NM_003070
Type: single nucleotide variant
Location: chr9:2029164 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 48: the 'disordered' region

Full SMARCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SMARCA2 p.Pro48Arg Uncertain significance ★ ⚠ same residue
SMARCA2 p.Ala1138Pro Pathogenic/Likely pathogenic ★★ same condition
SMARCA2 p.Arg505Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
SMARCA2 p.Ala1215Val Uncertain significance ★★ ⚠ same condition
SMARCA2 p.Ala1389Ser Uncertain significance ★★ ⚠ same condition
SMARCA2 p.Arg1266Gly Uncertain significance ★★ ⚠ same condition
SMARCA2 p.Arg427Cys Uncertain significance ★★ ⚠ same condition
SMARCA2 p.Glu1509Asp Uncertain significance ★★ ⚠ 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/smarca2-p-pro48ser (accessed [today's date]).

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