Is TSPEAR p.Phe413fs (c.1238_1239del) pathogenic?

TSPEAR p.Phe413fs (c.12381239del) is classified Pathogenic in TSPEAR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). Very rare (popmax 8.47e-05%, nfe); Associated with tooth agenesis, selective, 10.

How common is TSPEAR p.Phe413fs (c.1238_1239del) in the general population?

TSPEAR p.Phe413fs (c.1238_1239del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

TSPEAR p.Phe413fs

Q: What condition is associated with TSPEAR p.Phe413fs (c.1238_1239del)?

TSPEAR p.Phe413fs (c.1238_1239del) is associated with tooth agenesis, selective, 10, autosomal recessive nonsyndromic hearing loss 98, ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis (ClinVar).

c.1238_1239del · VCV4081842

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

tooth agenesis, selective, 10

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 8 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.3	GERP -3.1, phastCons 0.14

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,014 alleles

Overall 6.2e-05% 1/1,614,070 alleles · very rare exomes 1/1,461,884 · genomes 0/152,186 · 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: TSPEAR
Protein: p.Phe413fs
Coding: c.1238_1239del
MANE Select: NM_144991
Type: Deletion
Location: chr21:44525750 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.47
Residue 413: a UniProt-annotated variant site (in ectd14 and sthag10); a UniProt-annotated variant site (in ectd14)

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

Disease context

tooth agenesis, selective, 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive nonsyndromic hearing loss 98 ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis

Similar variants

TSPEAR p.Leu13fs Pathogenic/Likely pathogenic ★★ same condition
TSPEAR p.Pro393fs Pathogenic/Likely pathogenic ★★ same condition
TSPEAR p.Phe413Leu Uncertain significance ★★ ⚠ same residue
TSPEAR p.Glu480fs Pathogenic ★ same condition
TSPEAR p.Lys502fs Likely pathogenic ★ same condition
TSPEAR p.Ser483fs Likely pathogenic ★ same condition
TSPEAR c.923-220_1336+274del Uncertain significance ★ same condition
TSPEAR p.Gly17fs 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/tspear-p-phe413fs (accessed [today's date]).

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