Is TSC1 p.Ser671= (c.2013C>T) pathogenic?

TSC1 p.Ser671= (c.2013C>T) is classified Conflicting classifications of pathogenicity in TSC1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-06). Absent from gnomAD v4.1; Associated with tuberous sclerosis 1.

What condition is associated with TSC1 p.Ser671= (c.2013C>T)?

TSC1 p.Ser671= (c.2013C>T) is associated with tuberous sclerosis 1, hereditary neoplastic syndrome (ClinVar).

How common is TSC1 p.Ser671= (c.2013C>T) in the general population?

TSC1 p.Ser671= (c.2013C>T) is absent from gnomAD v4.1 (gnomAD).

How is Tuberous sclerosis complex inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

TSC1 p.Ser671=

c.2013C>T · rs1845545985 · VCV3231288

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

tuberous sclerosis 1

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
Pangolin	Δ0.26	loss · gain 0.03 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 8.4	GERP 1.8, phastCons 1
Overall
CADD	15.74	PHRED · no single calibrated threshold — expert panels disagree

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: TSC1
Protein: p.Ser671=
Coding: c.2013C>T
MANE Select: NM_000368
dbSNP: rs1845545985
Type: single nucleotide variant
Location: chr9:132904439 (GRCh38)
Gene constraint: LOEUF 0.227 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.55 · 5 PDB
Residue 671: the 'mediates interaction with wdr45b' region; an α-helix; a UniProt-annotated variant site (in tsc1)

Full TSC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

tuberous sclerosis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Tuberous sclerosis complex (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (Taiwan, Province of China)

Similar variants

TSC1 p.Ser671Asn Uncertain significance ★★ same residue
TSC1 p.Ser671Ile Uncertain significance ★★ ⚠ same residue
TSC1 p.Ser671Thr Uncertain significance ★★ ⚠ same residue
TSC1 p.Ser671Arg Uncertain significance ★ ⚠ same residue
TSC1 p.Ser671Gly Likely benign ★ ⚠ same residue
TSC1 p.Ser671fs Pathogenic ★ same residue
TSC1 c.1029+1G>A Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.1029+1G>C Pathogenic/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/tsc1-p-ser671 (accessed [today's date]).

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