Is TXLNA p.Ser232Arg (c.694A>C) pathogenic?

TXLNA p.Ser232Arg (c.694A>C) is classified Uncertain significance in TXLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-20). AlphaMissense: likely pathogenic (0.9661); Very rare (popmax 8.51e-05%, nfe).

How common is TXLNA p.Ser232Arg (c.694A>C) in the general population?

TXLNA p.Ser232Arg (c.694A>C) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

What do computational predictors say about TXLNA p.Ser232Arg (c.694A>C)?

AlphaMissense predicts likely pathogenic (score 0.9661) — an in-silico prediction, not a clinical call.

TXLNA p.Ser232Arg

c.694A>C · rs2523726363 · VCV2619581

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9661 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9661	likely pathogenic
REVEL	0.256	benign-leaning
SaProt	LLR -13.34	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 14 kb · p 5.4e-09 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.51e-05% European (non-Finnish) · 1/1,175,496 alleles

Overall 6.23e-05% 1/1,604,440 alleles · very rare exomes 1/1,452,094 · genomes 0/152,346 · 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: TXLNA
Protein: p.Ser232Arg
Coding: c.694A>C
MANE Select: NM_175852
dbSNP: rs2523726363
Type: single nucleotide variant
Location: chr1:32188050 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.29

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-ser232arg (accessed [today's date]).

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