Is TXNL4A p.Arg29Pro (c.86G>C) pathogenic?

TXNL4A p.Arg29Pro (c.86G>C) is classified Uncertain significance in TXNL4A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely pathogenic (0.9988); Very rare (popmax 0.00168%, amr); Associated with Inborn genetic diseases.

What condition is associated with TXNL4A p.Arg29Pro (c.86G>C)?

TXNL4A p.Arg29Pro (c.86G>C) is associated with Inborn genetic diseases (ClinVar).

How common is TXNL4A p.Arg29Pro (c.86G>C) in the general population?

TXNL4A p.Arg29Pro (c.86G>C) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about TXNL4A p.Arg29Pro (c.86G>C)?

AlphaMissense predicts likely pathogenic (score 0.9988) — an in-silico prediction, not a clinical call.

TXNL4A p.Arg29Pro

c.86G>C · VCV3464727

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9988 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9988	likely pathogenic
REVEL	0.714	pathogenic-leaning
SaProt	LLR -15.85	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP -0.67, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 15 kb · p 1.4e-08 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00168% Admixed American · 1/59,470 alleles

Overall 6.24e-05% 1/1,603,084 alleles · very rare exomes 1/1,450,722 · genomes 0/152,362 · 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.Arg29Pro
Coding: c.86G>C
MANE Select: NM_006701
Type: single nucleotide variant
Location: chr18:79988307 (GRCh38)
Gene constraint: LOEUF 1.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.21 · 32 PDB
Residue 29: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TXNL4A p.Asn87Ser Uncertain significance ★★ ⚠ same condition
TXNL4A p.Lys51Met Uncertain significance ★ same condition
TXNL4A p.Thr118Met Uncertain significance ★ ⚠ same condition
TXNL4A p.Val14Gly Uncertain significance ★ ⚠ same condition
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

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-arg29pro (accessed [today's date]).

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