Is TREH p.Asp256= (c.768C>T) pathogenic?

TREH p.Asp256= (c.768C>T) is classified Likely benign in TREH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-06-23). Very rare (popmax 0.00333%, amr); Associated with TREH-related disorder.

What condition is associated with TREH p.Asp256= (c.768C>T)?

TREH p.Asp256= (c.768C>T) is associated with TREH-related disorder (ClinVar).

How common is TREH p.Asp256= (c.768C>T) in the general population?

TREH p.Asp256= (c.768C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

TREH p.Asp256=

c.768C>T · rs782533738 · VCV3029924

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 3.2	GERP 0.86, phastCons 1
Overall
CADD	8.703	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,024 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,613,958 alleles · very rare exomes 2/1,461,690 · genomes 0/152,268 · joint denominator

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.Asp256=
Coding: c.768C>T
MANE Select: NM_007180
dbSNP: rs782533738
Type: single nucleotide variant
Location: chr11:118661249 (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.Arg83= 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-asp256 (accessed [today's date]).

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