Is TNXB p.Pro41= (c.123C>G) pathogenic?

TNXB p.Pro41= (c.123C>G) is classified Likely benign in TNXB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-21). Very rare (popmax 0.00112%, sas); Associated with Cardiovascular phenotype.

What condition is associated with TNXB p.Pro41= (c.123C>G)?

TNXB p.Pro41= (c.123C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is TNXB p.Pro41= (c.123C>G) in the general population?

TNXB p.Pro41= (c.123C>G) is very rare (popmax 0.00112%, sas) (gnomAD).

TNXB p.Pro41=

c.123C>G · rs1225724246 · VCV1757827

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00112%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.71	GERP -3.5
Overall
CADD	6.283	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% South Asian · 1/89,458 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000374% 6/1,605,872 alleles · very rare exomes 6/1,453,560 · genomes 0/152,312 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00112%	89,458
European (non-Finnish)	0.000425%	235,443

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: TNXB
Protein: p.Pro41=
Coding: c.123C>G
MANE Select: NM_001365276
dbSNP: rs1225724246
Type: single nucleotide variant
Location: chr6:32098076 (GRCh38)
Gene constraint: LOEUF 0.674 · pLI <0.01 (gnomAD)
Residue 41: the 'disordered' region

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TNXB p.Pro41Leu Uncertain significance ★ same residue
TNXB p.Arg821Ter Pathogenic/Likely pathogenic ★★ same condition
TNXB c.403+3G>A Uncertain significance ★★ same condition
TNXB c.4990+3G>A Uncertain significance ★★ same condition
TNXB c.9757+4A>G Uncertain significance ★★ same condition
TNXB p.Ala1231Val Uncertain significance ★★ ⚠ same condition
TNXB p.Ala1571Thr Uncertain significance ★★ ⚠ same condition
TNXB p.Ala1860Thr Uncertain significance ★★ ⚠ same condition

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/tnxb-p-pro41 (accessed [today's date]).

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