Is SMARCA1 p.Pro73Ser (c.217C>T) pathogenic?

SMARCA1 p.Pro73Ser (c.217C>T) is classified Uncertain significance in SMARCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-05). AlphaMissense: likely benign (0.0658); Absent from gnomAD v4.1.

How common is SMARCA1 p.Pro73Ser (c.217C>T) in the general population?

SMARCA1 p.Pro73Ser (c.217C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMARCA1 p.Pro73Ser (c.217C>T)?

AlphaMissense predicts likely benign (score 0.0658) — an in-silico prediction, not a clinical call.

SMARCA1 p.Pro73Ser

c.217C>T · VCV3899543

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0658 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0658	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -5.93	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 4.3	GERP 0.39, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 6,892 bp · p 0.02 · regional, not allelic
Overall
CADD	6.67	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

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: SMARCA1
Protein: p.Pro73Ser
Coding: c.217C>T
MANE Select: NM_001282874
Type: single nucleotide variant
Location: chrX:129518405 (GRCh38)
Structure: AlphaFold pLDDT 75.48
Residue 73: the 'disordered' region

Full SMARCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SMARCA1 p.Ala39Thr Uncertain significance ★★ ⚠ same type
SMARCA1 p.Ala48Glu Uncertain significance ★★ ⚠ same type
SMARCA1 p.Ala6Pro Uncertain significance ★★ ⚠ same type
SMARCA1 p.Arg751Gln Uncertain significance ★★ ⚠ same type
SMARCA1 p.Asp721Asn Uncertain significance ★★ same type
SMARCA1 p.Gly30Arg Uncertain significance ★★ ⚠ same type
SMARCA1 p.Lys680Glu Uncertain significance ★★ same type
SMARCA1 p.Met1028Ile Uncertain significance ★★ same type

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/smarca1-p-pro73ser (accessed [today's date]).

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