Is SMARCA5 p.Pro37Ser (c.109C>T) pathogenic?

SMARCA5 p.Pro37Ser (c.109C>T) is classified Uncertain significance in SMARCA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: likely benign (0.0694); Very rare (popmax 0.00501%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SMARCA5 p.Pro37Ser (c.109C>T)?

SMARCA5 p.Pro37Ser (c.109C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SMARCA5 p.Pro37Ser (c.109C>T) in the general population?

SMARCA5 p.Pro37Ser (c.109C>T) is very rare (popmax 0.00501%, nfe) (gnomAD).

What do computational predictors say about SMARCA5 p.Pro37Ser (c.109C>T)?

AlphaMissense predicts likely benign (score 0.0694) — an in-silico prediction, not a clinical call.

SMARCA5 p.Pro37Ser

c.109C>T · VCV3446040

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0694 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0694	likely benign
REVEL	0.233	benign-leaning
SaProt	LLR -4.76	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.3	GERP -0.38, phastCons 0.012
Regional constraint	o/e 1.28	unconstrained · MANE · 7,517 bp · p 0.0017 · regional, not allelic
Overall
CADD	13.88	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00501% European (non-Finnish) · 58/1,158,346 alleles

Filtering AF 0.00393% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00359%

Overall 0.00379% 59/1,555,000 alleles · very rare exomes 54/1,402,638 · genomes 5/152,362 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00501%	19,971
Remaining individualsnot grpmax-eligible	0.00165%	60,686

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: SMARCA5
Protein: p.Pro37Ser
Coding: c.109C>T
MANE Select: NM_003601
Type: single nucleotide variant
Location: chr4:143514033 (GRCh38)
Gene constraint: LOEUF 0.222 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.41 · 15 PDB
Residue 37: the 'disordered' region

Full SMARCA5 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

SMARCA5 p.Lys694Glu Uncertain significance ★★ ⚠ same condition
SMARCA5 p.Met386Thr Uncertain significance ★★ ⚠ same condition
SMARCA5 p.Ala44Val Uncertain significance ★ ⚠ same condition
SMARCA5 p.Ala48Gly Uncertain significance ★ ⚠ same condition
SMARCA5 p.Ala49Val Uncertain significance ★ ⚠ same condition
SMARCA5 p.Ala51Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
SMARCA5 p.Ala51Val Uncertain significance ★ ⚠ same condition
SMARCA5 p.Ala5Ser 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/smarca5-p-pro37ser (accessed [today's date]).

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