Is TECTA p.Cys1072= (c.3216C>T) pathogenic?

TECTA p.Cys1072= (c.3216C>T) is classified Uncertain significance in TECTA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-09-24). Ultra-rare (popmax 0.0178%, eas); Associated with autosomal dominant nonsyndromic hearing loss 12.

What condition is associated with TECTA p.Cys1072= (c.3216C>T)?

TECTA p.Cys1072= (c.3216C>T) is associated with autosomal dominant nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 21 (ClinVar).

How common is TECTA p.Cys1072= (c.3216C>T) in the general population?

TECTA p.Cys1072= (c.3216C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

TECTA p.Cys1072=

c.3216C>T · rs760328639 · VCV303014

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.29	GERP -3.2, phastCons 0.38
Overall
CADD	7.352	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,864 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00652%

Overall 0.00737% 119/1,613,926 alleles · ultra-rare exomes 109/1,461,884 · genomes 10/152,042 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,608
Remaining individualsnot grpmax-eligible	0.0144%	6,943
European (non-Finnish)	0.00839%	11,919
African / African-American	0.00401%	24,957

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.Cys1072=
Coding: c.3216C>T
MANE Select: NM_005422
dbSNP: rs760328639
Type: single nucleotide variant
Location: chr11:121137695 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.64

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.Cys1402Ser 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-cys1072 (accessed [today's date]).

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