Is TECPR2 p.Thr189fs (c.565_569del) pathogenic?

TECPR2 p.Thr189fs (c.565569del) is classified Likely pathogenic in TECPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-01). Very rare (popmax 0.0011%, sas).

How common is TECPR2 p.Thr189fs (c.565_569del) in the general population?

TECPR2 p.Thr189fs (c.565_569del) is very rare (popmax 0.0011%, sas) (gnomAD).

TECPR2 p.Thr189fs

c.565_569del · rs1595112176 · VCV807179

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Overall 6.19e-05% 1/1,614,222 alleles · very rare exomes 1/1,461,890 · genomes 0/152,332 · 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: TECPR2
Protein: p.Thr189fs
Coding: c.565_569del
MANE Select: NM_014844
dbSNP: rs1595112176
Type: Deletion
Location: chr14:102414716 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.27

Full TECPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TECPR2 p.Thr189Ile Uncertain significance ★ ⚠ same residue
TECPR2 c.222delG Pathogenic/Likely pathogenic ★★ same type
TECPR2 p.Asn1277fs Pathogenic/Likely pathogenic ★★ same type
TECPR2 p.Asn944fs Pathogenic/Likely pathogenic ★★ same type
TECPR2 p.Asp259fs Pathogenic/Likely pathogenic ★★ same type
TECPR2 p.Gln1263fs Pathogenic/Likely pathogenic ★★ same type
TECPR2 p.Gly584fs Pathogenic/Likely pathogenic ★★ same type
TECPR2 p.Leu1139fs Pathogenic ★★ same type

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/tecpr2-p-thr189fs (accessed [today's date]).

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