Is TECTA p.His2023= (c.6069C>T) pathogenic?

TECTA p.His2023= (c.6069C>T) is classified Uncertain significance in TECTA (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-23). Ultra-rare (popmax 0.0209%, sas); Associated with autosomal dominant nonsyndromic hearing loss 12.

What condition is associated with TECTA p.His2023= (c.6069C>T)?

TECTA p.His2023= (c.6069C>T) is associated with autosomal dominant nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 21 (ClinVar).

How common is TECTA p.His2023= (c.6069C>T) in the general population?

TECTA p.His2023= (c.6069C>T) is ultra-rare (popmax 0.0209%, sas) (gnomAD).

TECTA p.His2023=

c.6069C>T · rs759915442 · VCV877889

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, sas)

Conditions

autosomal dominant nonsyndromic hearing loss 12

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -12	GERP -3.7
Overall
CADD	7.817	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0209% South Asian · 19/91,086 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.00359% 58/1,614,116 alleles · ultra-rare exomes 54/1,461,886 · genomes 4/152,230 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0209%	4,794
Middle Eastern	0.0164%	6,084
East Asian	0.0134%	7,484
Admixed American	0.005%	20,004
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)	0.0022%	45,386
African / African-American	0.00133%	74,946

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: TECTA
Protein: p.His2023=
Coding: c.6069C>T
MANE Select: NM_005422
dbSNP: rs759915442
Type: single nucleotide variant
Location: chr11:121187901 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.64
Residue 2023: the zp domain

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

Disease context

autosomal dominant nonsyndromic hearing loss 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive nonsyndromic hearing loss 21

Similar variants

TECTA p.Arg371Gly Benign ★★★ same condition
TECTA c.2367+2T>C Likely pathogenic ★★ same condition
TECTA c.4690-1G>A Pathogenic/Likely pathogenic ★★ same condition
TECTA p.Arg1174Ter Pathogenic ★★ same condition
TECTA p.Ala567Thr Uncertain significance ★★ ⚠ same condition
TECTA p.Arg284Cys Uncertain significance ★★ ⚠ same condition
TECTA p.Arg474Cys Uncertain significance ★★ ⚠ same condition
TECTA p.Cys1072= 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/tecta-p-his2023 (accessed [today's date]).

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