Is TNXB p.Pro2000= (c.6000T>C) pathogenic?

TNXB p.Pro2000= (c.6000T>C) is classified Likely benign in TNXB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-24). Very rare (popmax 0.00223%, eas); Associated with Cardiovascular phenotype.

What condition is associated with TNXB p.Pro2000= (c.6000T>C)?

TNXB p.Pro2000= (c.6000T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is TNXB p.Pro2000= (c.6000T>C) in the general population?

TNXB p.Pro2000= (c.6000T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

TNXB p.Pro2000=

c.6000T>C · VCV3327943

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 -20	GERP -4.1
Overall
CADD	0.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,862 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,613,844 alleles · very rare exomes 5/1,461,630 · genomes 0/152,214 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,862
South Asian	0.0011%	91,064
European (non-Finnish)	0.000254%	393,278

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.Pro2000=
Coding: c.6000T>C
MANE Select: NM_001365276
Type: single nucleotide variant
Location: chr6:32068610 (GRCh38)
Gene constraint: LOEUF 0.674 · pLI <0.01 (gnomAD)
Residue 2000: the fibronectin type-iii 13 domain

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.Pro2000Ser 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-pro2000 (accessed [today's date]).

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