Is TSHR p.Ala593fs (c.1777del) pathogenic?

TSHR p.Ala593fs (c.1777del) is classified Likely pathogenic in TSHR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-22). No gnomAD frequency available for this variant; Associated with hypothyroidism due to TSH receptor mutations.

What condition is associated with TSHR p.Ala593fs (c.1777del)?

TSHR p.Ala593fs (c.1777del) is associated with hypothyroidism due to TSH receptor mutations (ClinVar).

How common is TSHR p.Ala593fs (c.1777del) in the general population?

TSHR p.Ala593fs (c.1777del) is no gnomAD frequency available for this variant (gnomAD).

How is Hypothyroidism due to TSH receptor mutations inherited?

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

TSHR p.Ala593fs

c.1777del · rs2140112570 · VCV1687384

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hypothyroidism due to TSH receptor mutations

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -7.7	GERP -8.3

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TSHR
Protein: p.Ala593fs
Coding: c.1777del
dbSNP: rs2140112570
Type: Deletion
Location: chr14:81143835 (GRCh38)

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

Disease context

hypothyroidism due to TSH receptor mutations — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hypothyroidism due to TSH receptor mutations (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal

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/tshr-p-ala593fs (accessed [today's date]).

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