Is TXLNA p.Pro34Ser (c.100C>T) pathogenic?

TXLNA p.Pro34Ser (c.100C>T) is classified Uncertain significance in TXLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-12). AlphaMissense: likely benign (0.0742); Absent from gnomAD v4.1.

How common is TXLNA p.Pro34Ser (c.100C>T) in the general population?

TXLNA p.Pro34Ser (c.100C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TXLNA p.Pro34Ser (c.100C>T)?

AlphaMissense predicts likely benign (score 0.0742) — an in-silico prediction, not a clinical call.

TXLNA p.Pro34Ser

c.100C>T · rs2523686763 · VCV2204308

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0742 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0742	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.24	GERP 2.2, phastCons 0.95
Regional constraint	o/e 1.04	unconstrained · MANE · 1,158 bp · p 0.6 · regional, not allelic
Overall
CADD	16.91	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TXLNA
Protein: p.Pro34Ser
Coding: c.100C>T
MANE Select: NM_175852
dbSNP: rs2523686763
Type: single nucleotide variant
Location: chr1:32180445 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.29
Residue 34: the 'disordered' region

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

Similar variants

TXLNA p.Ser514Arg Benign ★★ same type
TXLNA c.1251+1G>C Uncertain significance ★ same type
TXLNA c.963+1G>C Uncertain significance ★ same type
TXLNA p.Ala105Thr Uncertain significance ★ ⚠ same type
TXLNA p.Ala38Ser Uncertain significance ★ ⚠ same type
TXLNA p.Ala473Gly Uncertain significance ★ ⚠ same type
TXLNA p.Ala544Pro Uncertain significance ★ ⚠ same type
TXLNA p.Arg228His 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/txlna-p-pro34ser (accessed [today's date]).

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