Is TNXB p.Pro2010= (c.6030C>T) pathogenic?

TNXB p.Pro2010= (c.6030C>T) is classified Benign in TNXB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 34%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with TNXB p.Pro2010= (c.6030C>T)?

TNXB p.Pro2010= (c.6030C>T) is associated with Cardiovascular phenotype (ClinVar).

TNXB p.Pro2010=

Q: How common is TNXB p.Pro2010= (c.6030C>T) in the general population?

TNXB p.Pro2010= (c.6030C>T) is common (popmax 34%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6030C>T · rs3749962 · VCV261144

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 34%, sas) — too common for a highly-penetrant pathogenic allele

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 -11	GERP -4.1
Overall
CADD	0.985	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 34% South Asian · 30,994/91,074 alleles

Filtering AF 33.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 33.6%

Overall 11.5% 185,564/1,613,830 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	34%	3
Middle Eastern	26.7%	4
African / African-American	25.3%	4
Remaining individualsnot grpmax-eligible	12.7%	8
Admixed American	11.4%	9
Ashkenazi Jewishnot grpmax-eligible	10.9%	9
East Asian	10.9%	9
European (non-Finnish)	9.05%	11
Finnishnot grpmax-eligible	6.75%	15
Amishnot grpmax-eligible	1.64%	61

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.Pro2010=
Coding: c.6030C>T
MANE Select: NM_001365276
dbSNP: rs3749962
Type: single nucleotide variant
Location: chr6:32068580 (GRCh38)
Gene constraint: LOEUF 0.674 · pLI <0.01 (gnomAD)
Residue 2010: 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.Pro2010Arg 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-pro2010 (accessed [today's date]).

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