Is TXNL4A p.Phe30fs (c.88_110del) pathogenic?

TXNL4A p.Phe30fs (c.88110del) is classified Likely pathogenic in TXNL4A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-11). Very rare (popmax 8.52e-05%, nfe); Associated with TXNL4A-related disorder.

What condition is associated with TXNL4A p.Phe30fs (c.88_110del)?

TXNL4A p.Phe30fs (c.88_110del) is associated with TXNL4A-related disorder, choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome (ClinVar).

How common is TXNL4A p.Phe30fs (c.88_110del) in the general population?

TXNL4A p.Phe30fs (c.88_110del) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

TXNL4A p.Phe30fs

c.88_110del · rs1555719172 · VCV451615

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

Conditions

TXNL4A-related disorder

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 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.9	GERP -3

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.52e-05% European (non-Finnish) · 1/1,173,158 alleles

Overall 6.23e-05% 1/1,603,852 alleles · very rare exomes 1/1,451,470 · genomes 0/152,382 · 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: TXNL4A
Protein: p.Phe30fs
Coding: c.88_110del
MANE Select: NM_006701
dbSNP: rs1555719172
Type: Deletion
Location: chr18:79988283 (GRCh38)
Gene constraint: LOEUF 1.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.21 · 32 PDB
Residue 30: a β-strand

Full TXNL4A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TXNL4A-related disorder

Also linked: choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome

Similar variants

TXNL4A c.Exon Pathogenic same condition
TXNL4A p.Asn87Alafs Pathogenic same condition
TXNL4A p.His32fs Pathogenic same condition
TXNL4A p.Asn87Ser Uncertain significance ★★ ⚠ same condition
TXNL4A p.Val25Glu Uncertain significance ★★ ⚠ same condition
TXNL4A p.Arg141= Benign/Likely benign ★★ same condition
TXNL4A p.Gly97fs Likely pathogenic ★ same condition
TXNL4A c.-61+1G>A Uncertain significance ★ 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/txnl4a-p-phe30fs (accessed [today's date]).

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