Is TXNL4A p.Arg141= (c.423C>T) pathogenic?

TXNL4A p.Arg141= (c.423C>T) is classified Benign/Likely benign in TXNL4A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-03-01). Rare (popmax 0.891%, mid); Associated with choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome.

How common is TXNL4A p.Arg141= (c.423C>T) in the general population?

TXNL4A p.Arg141= (c.423C>T) is rare (popmax 0.891%, mid) (gnomAD).

TXNL4A p.Arg141=

Q: What condition is associated with TXNL4A p.Arg141= (c.423C>T)?

TXNL4A p.Arg141= (c.423C>T) is associated with choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome (ClinVar).

c.423C>T · rs143131944 · VCV722554

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.891%, mid)

Conditions

choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.54	GERP -3.9, phastCons 0.15
Overall
CADD	3.907	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.891% Middle Eastern · 54/6,058 alleles

Filtering AF 0.702% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.634%

Overall 0.0905% 1,460/1,612,474 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.891%	112
South Asian	0.554%	180
Ashkenazi Jewishnot grpmax-eligible	0.403%	248
Remaining individualsnot grpmax-eligible	0.146%	686
European (non-Finnish)	0.0554%	1,806
Admixed American	0.047%	2,127
African / African-American	0.0133%	7,497
Finnishnot grpmax-eligible	0.00312%	32,008

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.Arg141=
Coding: c.423C>T
MANE Select: NM_006701
dbSNP: rs143131944
Type: single nucleotide variant
Location: chr18:79973691 (GRCh38)
Gene constraint: LOEUF 1.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.21 · 32 PDB

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

Disease context

choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TXNL4A p.Asn87Ser Uncertain significance ★★ ⚠ same condition
TXNL4A p.Val25Glu Uncertain significance ★★ ⚠ same condition
TXNL4A c.-61+1G>A Uncertain significance ★ same condition
TXNL4A p.Pro67Ser Uncertain significance ★ ⚠ same condition
TXNL4A c.258-3C>G Pathogenic same condition
TXNL4A p.Phe30fs Likely pathogenic ★★ same condition
TXNL4A p.Gly97fs Likely pathogenic ★ same condition
TXNL4A c.Exon 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/txnl4a-p-arg141 (accessed [today's date]).

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