Is TSC2 p.Phe1510= (c.4530T>C) pathogenic?

TSC2 p.Phe1510= (c.4530T>C) is classified Benign/Likely benign in TSC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-04). Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with TSC2 p.Phe1510= (c.4530T>C)?

TSC2 p.Phe1510= (c.4530T>C) is associated with hereditary neoplastic syndrome, tuberous sclerosis 2 (ClinVar).

How common is TSC2 p.Phe1510= (c.4530T>C) in the general population?

TSC2 p.Phe1510= (c.4530T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

TSC2 p.Phe1510=

c.4530T>C · rs763126313 · VCV2162499

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.85 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.1	GERP -3.5
Overall
CADD	1.325	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,872 alleles

Overall 0.000124% 2/1,613,138 alleles · very rare exomes 2/1,460,882 · genomes 0/152,256 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,872
European (non-Finnish)	8.47e-05%	1,179,954

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TSC2
Protein: p.Phe1510=
Coding: c.4530T>C
MANE Select: NM_000548
dbSNP: rs763126313
Type: single nucleotide variant
Location: chr16:2084987 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB

Full TSC2 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 2

Similar variants

TSC2 p.Phe1510Ile Uncertain significance ★ ⚠ same residue
TSC2 p.Phe1510Leu Uncertain significance ★ ⚠ same residue
TSC2 p.Phe1510Ser Uncertain significance ★ ⚠ same residue
TSC2 p.Phe1510Tyr Uncertain significance ★ ⚠ same residue
TSC2 p.Phe1510_Gly1511delinsLeuCys Uncertain significance ★ same residue
TSC2 p.Phe1510del Conflicting classifications of pathogenicity ★ same residue
TSC2 c.1257+1G>A Pathogenic ★★ same condition
TSC2 c.1258-2A>G 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/tsc2-p-phe1510 (accessed [today's date]).

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