Is TSC1 p.Val220= (c.660C>G) pathogenic?

TSC1 p.Val220= (c.660C>G) is classified Benign/Likely benign in TSC1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-08). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with TSC1 p.Val220= (c.660C>G)?

TSC1 p.Val220= (c.660C>G) is associated with hereditary neoplastic syndrome, tuberous sclerosis 1 (ClinVar).

How common is TSC1 p.Val220= (c.660C>G) in the general population?

TSC1 p.Val220= (c.660C>G) is absent from gnomAD v4.1 (gnomAD).

TSC1 p.Val220=

c.660C>G · rs1588346808 · VCV1537790

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

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
Constraint at this position
Conservation	phyloP 7.1	GERP 0.11, phastCons 1
Overall
CADD	10.96	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.Val220=
Coding: c.660C>G
MANE Select: NM_000368
dbSNP: rs1588346808
Type: single nucleotide variant
Location: chr9:132921822 (GRCh38)
Gene constraint: LOEUF 0.227 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.55 · 5 PDB
Residue 220: a UniProt-annotated variant site (in tsc1); an α-helix

Full TSC1 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

Also linked: tuberous sclerosis 1

Similar variants

TSC1 p.Val220Asp Likely pathogenic ★ same residue
TSC1 p.Val220Gly Uncertain significance ★ ⚠ same residue
TSC1 p.Val220Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
TSC1 p.Val220Leu Uncertain significance ★ ⚠ same residue
TSC1 c.1029+1G>A Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.1029+1G>C Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.107-1G>A Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.1141+1G>A 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-val220 (accessed [today's date]).

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