Is THRA p.Arg372Ter (c.1114A>T) pathogenic?

THRA p.Arg372Ter (c.1114A>T) is classified Uncertain significance in THRA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). Very rare (popmax 0.00484%, nfe); Associated with Inborn genetic diseases.

What condition is associated with THRA p.Arg372Ter (c.1114A>T)?

THRA p.Arg372Ter (c.1114A>T) is associated with Inborn genetic diseases (ClinVar).

How common is THRA p.Arg372Ter (c.1114A>T) in the general population?

THRA p.Arg372Ter (c.1114A>T) is very rare (popmax 0.00484%, nfe) (gnomAD).

THRA p.Arg372Ter

c.1114A>T · rs201029306 · VCV2214705

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00484%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	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 9.1	GERP 1.6, phastCons 1
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00484% European (non-Finnish) · 57/1,176,784 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00346%

Overall 0.00366% 59/1,610,114 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00484%	20,645
Remaining individualsnot grpmax-eligible	0.0016%	62,318
African / African-American	0.00134%	74,802

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: THRA
Protein: p.Arg372Ter
Coding: c.1114A>T
MANE Select: NM_021724 · reported on NM_003250
dbSNP: rs201029306
Type: single nucleotide variant
Location: chr17:40093023 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/thra-p-arg372ter (accessed [today's date]).

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