Is TXNL4A p.Ile28= (c.84C>T) pathogenic?

TXNL4A p.Ile28= (c.84C>T) is classified Likely benign in TXNL4A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-06). Ultra-rare (popmax 0.0241%, afr); Associated with TXNL4A-related disorder.

What condition is associated with TXNL4A p.Ile28= (c.84C>T)?

TXNL4A p.Ile28= (c.84C>T) is associated with TXNL4A-related disorder (ClinVar).

How common is TXNL4A p.Ile28= (c.84C>T) in the general population?

TXNL4A p.Ile28= (c.84C>T) is ultra-rare (popmax 0.0241%, afr) (gnomAD).

TXNL4A p.Ile28=

c.84C>T · rs757909492 · VCV3044113

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0241%, afr)

Conditions

TXNL4A-related disorder

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 -0.32	GERP -3, phastCons 0.001
Overall
CADD	5.134	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0241% African / African-American · 18/74,662 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00137% 22/1,603,748 alleles · ultra-rare exomes 13/1,451,484 · genomes 9/152,264 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0241%	4,148
Remaining individualsnot grpmax-eligible	0.00323%	30,963
South Asian	0.00112%	89,664
European (non-Finnish)	8.51e-05%	1,174,400

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.Ile28=
Coding: c.84C>T
MANE Select: NM_006701
dbSNP: rs757909492
Type: single nucleotide variant
Location: chr18:79988309 (GRCh38)
Gene constraint: LOEUF 1.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.21 · 32 PDB
Residue 28: a β-strand

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

Disease context

TXNL4A-related disorder

Similar variants

TXNL4A p.Ala56= Likely benign same condition
TXNL4A p.Phe30fs Likely pathogenic ★★ same condition
TXNL4A p.Asn87Ser Uncertain significance ★★ ⚠ same type
TXNL4A p.Val25Glu Uncertain significance ★★ ⚠ same type
TXNL4A c.153+1617A>G Benign ★★ same type
TXNL4A c.257+201G>A Benign ★★ same type
TXNL4A p.Arg141= Benign/Likely benign ★★ same type
TXNL4A c.-61+1G>A Uncertain significance ★ 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/txnl4a-p-ile28 (accessed [today's date]).

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