Is SMARCE1 p.Ser136Pro (c.406T>C) pathogenic?

SMARCE1 p.Ser136Pro (c.406T>C) is classified Uncertain significance in SMARCE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-25). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCE1 p.Ser136Pro (c.406T>C)?

SMARCE1 p.Ser136Pro (c.406T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SMARCE1 p.Ser136Pro (c.406T>C) in the general population?

SMARCE1 p.Ser136Pro (c.406T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMARCE1 p.Ser136Pro (c.406T>C)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

SMARCE1 p.Ser136Pro

c.406T>C · VCV3320848

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic · top 9% in SMARCE1
REVEL	0.807	moderately pathogenic-leaning
SaProt	LLR -13.05	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 388 bp · p 7.3e-05 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: SMARCE1
Protein: p.Ser136Pro
Coding: c.406T>C
MANE Select: NM_003079
Type: single nucleotide variant
Location: chr17:40636066 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.72 · 8 PDB

Full SMARCE1 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

Similar variants

SMARCE1 p.Ser136Ala Uncertain significance ★ ⚠ same residue
SMARCE1 p.Arg158Ter Pathogenic ★★ same condition
SMARCE1 p.Arg239Ter Pathogenic ★★ same condition
SMARCE1 p.Arg251Ter Pathogenic/Likely pathogenic ★★ same condition
SMARCE1 p.Gln225Ter Pathogenic ★★ same condition
SMARCE1 p.Glu110Ter Pathogenic ★★ same condition
SMARCE1 p.Glu165Ter Pathogenic ★★ same condition
SMARCE1 c.1027+5C>G 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/smarce1-p-ser136pro (accessed [today's date]).

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