Is TSC2 p.Gln370= (c.1110G>A) pathogenic?

TSC2 p.Gln370= (c.1110G>A) is classified Benign/Likely benign in TSC2 (ClinVar, Multiple submitters, 25 submitters; last evaluated 2026-07-01). Common (popmax 5.04%, mid) — too common for a highly-penetrant pathogenic allele; Associated with lymphangioleiomyomatosis.

What condition is associated with TSC2 p.Gln370= (c.1110G>A)?

TSC2 p.Gln370= (c.1110G>A) is associated with lymphangioleiomyomatosis, tuberous sclerosis, isolated focal cortical dysplasia type II (ClinVar).

TSC2 p.Gln370=

Q: How common is TSC2 p.Gln370= (c.1110G>A) in the general population?

TSC2 p.Gln370= (c.1110G>A) is common (popmax 5.04%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1110G>A · rs1800742 · VCV49141

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 25 submitters

gnomAD v4.1

Common

common (popmax 5.04%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

lymphangioleiomyomatosis

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 3.9	GERP 1.9, phastCons 1
Overall
CADD	7.839	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.04% Middle Eastern · 304/6,032 alleles

Filtering AF 4.57% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.39%

Overall 1.06% 17,089/1,613,538 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	5.04%	20
Ashkenazi Jewishnot grpmax-eligible	3.17%	32
Remaining individualsnot grpmax-eligible	1.28%	78
European (non-Finnish)	1.15%	87
Admixed American	0.62%	161
Finnishnot grpmax-eligible	0.613%	163
South Asian	0.534%	187
African / African-American	0.225%	444
Amishnot grpmax-eligible	0.11%	912
East Asian	0.00223%	44,870

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.Gln370=
Coding: c.1110G>A
MANE Select: NM_000548
dbSNP: rs1800742
Type: single nucleotide variant
Location: chr16:2060804 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 370: an α-helix; the 'required for interaction with tsc1' region

Full TSC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

lymphangioleiomyomatosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: tuberous sclerosis isolated focal cortical dysplasia type II tuberous sclerosis 2 hereditary neoplastic syndrome

For Perivascular epithelioid cell neoplasm (Orphanet):

Onset: Adolescent, Adult, Childhood, Elderly

Similar variants

TSC2 p.Gln370Ter Pathogenic ★★ same residue
TSC2 c.1257+1G>A Pathogenic ★★ same condition
TSC2 c.1258-2A>G Pathogenic ★★ same condition
TSC2 c.1361+1G>A Pathogenic/Likely pathogenic ★★ same condition
TSC2 c.1361+1G>T Pathogenic/Likely pathogenic ★★ same condition
TSC2 c.1362-1G>A Pathogenic ★★ same condition
TSC2 c.138+2T>C Pathogenic ★★ same condition
TSC2 c.138+5G>A 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/tsc2-p-gln370 (accessed [today's date]).

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