Is TREH p.Arg83= (c.249G>A) pathogenic?

TREH p.Arg83= (c.249G>A) is classified Likely benign in TREH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-10-21). Ultra-rare (popmax 0.0227%, afr); Associated with TREH-related disorder.

What condition is associated with TREH p.Arg83= (c.249G>A)?

TREH p.Arg83= (c.249G>A) is associated with TREH-related disorder (ClinVar).

How common is TREH p.Arg83= (c.249G>A) in the general population?

TREH p.Arg83= (c.249G>A) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

TREH p.Arg83=

c.249G>A · rs781987530 · VCV3043327

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Conditions

TREH-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.3	GERP -0.48
Overall
CADD	0.696	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0227% African / African-American · 17/74,912 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.00192% 31/1,613,792 alleles · ultra-rare exomes 19/1,461,620 · genomes 12/152,172 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,407
Remaining individualsnot grpmax-eligible	0.0032%	31,228
European (non-Finnish)	0.00102%	98,324

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: TREH
Protein: p.Arg83=
Coding: c.249G>A
MANE Select: NM_007180
dbSNP: rs781987530
Type: single nucleotide variant
Location: chr11:118663138 (GRCh38)
Gene constraint: LOEUF 1.19 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.80

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

Disease context

TREH-related disorder

Similar variants

TREH c.423+6A>T Likely benign same condition
TREH c.424-9C>T Likely benign same condition
TREH p.Ala385= Likely benign same condition
TREH p.Arg215= Likely benign same condition
TREH p.Asp256= Likely benign same condition
TREH p.Cys354= Likely benign same condition
TREH p.Glu37= Likely benign same condition
TREH p.Glu64= Likely benign 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/treh-p-arg83 (accessed [today's date]).

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