Is TXNL4A p.Ala56= (c.168A>G) pathogenic?

TXNL4A p.Ala56= (c.168A>G) is classified Likely benign in TXNL4A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-26). Ultra-rare (popmax 0.0139%, amr); Associated with TXNL4A-related disorder.

What condition is associated with TXNL4A p.Ala56= (c.168A>G)?

TXNL4A p.Ala56= (c.168A>G) is associated with TXNL4A-related disorder (ClinVar).

How common is TXNL4A p.Ala56= (c.168A>G) in the general population?

TXNL4A p.Ala56= (c.168A>G) is ultra-rare (popmax 0.0139%, amr) (gnomAD).

TXNL4A p.Ala56=

c.168A>G · rs762744869 · VCV3040549

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0139%, amr)

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 -0.19	GERP 0.96, phastCons 0.7
Overall
CADD	10.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0139% Admixed American · 8/57,624 alleles

Filtering AF 0.00685% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00499%

Overall 0.000687% 11/1,600,224 alleles · ultra-rare exomes 10/1,448,254 · genomes 1/151,970 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0139%	7,203
Remaining individualsnot grpmax-eligible	0.00323%	31,005
European (non-Finnish)	8.53e-05%	1,172,572

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.Ala56=
Coding: c.168A>G
MANE Select: NM_006701
dbSNP: rs762744869
Type: single nucleotide variant
Location: chr18:79977687 (GRCh38)
Gene constraint: LOEUF 1.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.21 · 32 PDB
Residue 56: 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.Ile28= 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-ala56 (accessed [today's date]).

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