Is THRB p.Arg438fs (c.1312del) pathogenic?

THRB p.Arg438fs (c.1312del) is classified Pathogenic in THRB (ClinVar, No assertion criteria, 2 submitters; last evaluated 2013-02-22). Absent from gnomAD; Associated with thyroid hormone resistance, generalized, autosomal dominant.

What condition is associated with THRB p.Arg438fs (c.1312del)?

THRB p.Arg438fs (c.1312del) is associated with thyroid hormone resistance, generalized, autosomal dominant (ClinVar).

How common is THRB p.Arg438fs (c.1312del) in the general population?

THRB p.Arg438fs (c.1312del) is absent from gnomAD (gnomAD).

THRB p.Arg438fs

c.1312del · rs1553609179 · VCV492922

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

thyroid hormone resistance, generalized, autosomal dominant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1

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: THRB
Protein: p.Arg438fs
Coding: c.1312del
MANE Select: NM_001354712
dbSNP: rs1553609179
Type: Deletion
Location: chr3:24122958 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.24 · 34 PDB
Residue 438: the nr lbd domain; a UniProt-annotated variant site (in grthd); the 'interaction with nr2f6' region; an α-helix

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

Disease context

thyroid hormone resistance, generalized, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

THRB p.Arg438Cys Pathogenic/Likely pathogenic ★★ ⚠ same residue
THRB p.Arg438His Pathogenic ★★ ⚠ same residue
THRB p.Thr337del Pathogenic ★ same condition
THRB p.Ala268Gly Pathogenic/Likely pathogenic ★★ same condition
THRB p.Ala317Thr Pathogenic ★★ same condition
THRB p.Arg316His Pathogenic ★★ same condition
THRB p.Arg320Cys Pathogenic ★★ same condition
THRB p.Arg320His 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/thrb-p-arg438fs (accessed [today's date]).

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