Is TSC1 p.Ser16Phe (c.47C>T) pathogenic?

TSC1 p.Ser16Phe (c.47C>T) is classified Uncertain significance in TSC1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-21). AlphaMissense: ambiguous (0.5241); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with TSC1 p.Ser16Phe (c.47C>T)?

TSC1 p.Ser16Phe (c.47C>T) is associated with hereditary neoplastic syndrome, tuberous sclerosis, tuberous sclerosis 1 (ClinVar).

How common is TSC1 p.Ser16Phe (c.47C>T) in the general population?

TSC1 p.Ser16Phe (c.47C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TSC1 p.Ser16Phe (c.47C>T)?

AlphaMissense predicts ambiguous (score 0.5241) — an in-silico prediction, not a clinical call.

TSC1 p.Ser16Phe

c.47C>T · rs774900322 · VCV534473

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.5241 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5241	ambiguous
REVEL	0.642	indeterminate
SaProt	LLR -10.76	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 23 kb · p 5.3e-09 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

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: TSC1
Protein: p.Ser16Phe
Coding: c.47C>T
MANE Select: NM_000368
dbSNP: rs774900322
Type: single nucleotide variant
Location: chr9:132928826 (GRCh38)
Gene constraint: LOEUF 0.227 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.55 · 5 PDB

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 tuberous sclerosis 1

Similar variants

TSC1 p.Ser16Cys Uncertain significance ★★ ⚠ same residue
TSC1 p.Ser16= Benign/Likely benign ★★ same residue
TSC1 p.Ser16Pro Uncertain significance ★ ⚠ same residue
TSC1 p.Ser16Tyr 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-ser16phe (accessed [today's date]).

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