Is TNXB p.Pro1982= (c.5946C>T) pathogenic?

TNXB p.Pro1982= (c.5946C>T) is classified Likely benign in TNXB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-14). Very rare (popmax 0.00415%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with TNXB p.Pro1982= (c.5946C>T)?

TNXB p.Pro1982= (c.5946C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is TNXB p.Pro1982= (c.5946C>T) in the general population?

TNXB p.Pro1982= (c.5946C>T) is very rare (popmax 0.00415%, nfe) (gnomAD).

TNXB p.Pro1982=

c.5946C>T · rs568504579 · VCV1750640

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00415%, nfe)

Conditions

Cardiovascular phenotype

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 -4.1	GERP -3
Overall
CADD	0.808	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00415% European (non-Finnish) · 49/1,179,866 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00335% 54/1,613,798 alleles · very rare exomes 48/1,461,612 · genomes 6/152,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00415%	24,079
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Remaining individualsnot grpmax-eligible	0.0032%	31,233
South Asian	0.0022%	45,539

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.Pro1982=
Coding: c.5946C>T
MANE Select: NM_001365276
dbSNP: rs568504579
Type: single nucleotide variant
Location: chr6:32068664 (GRCh38)
Gene constraint: LOEUF 0.674 · pLI <0.01 (gnomAD)
Residue 1982: 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.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
TNXB p.Ala1874Thr 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-pro1982 (accessed [today's date]).

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