Is TECTA p.Ser140= (c.420T>C) pathogenic?

TECTA p.Ser140= (c.420T>C) is classified Conflicting classifications of pathogenicity in TECTA (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-01-09). Ultra-rare (popmax 0.0579%, eas); Associated with autosomal dominant nonsyndromic hearing loss 12.

What condition is associated with TECTA p.Ser140= (c.420T>C)?

TECTA p.Ser140= (c.420T>C) is associated with autosomal dominant nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 21 (ClinVar).

How common is TECTA p.Ser140= (c.420T>C) in the general population?

TECTA p.Ser140= (c.420T>C) is ultra-rare (popmax 0.0579%, eas) (gnomAD).

TECTA p.Ser140=

c.420T>C · rs141090151 · VCV880300

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0579%, eas)

Conditions

autosomal dominant nonsyndromic hearing loss 12

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.4	GERP 0.33, phastCons 1
Overall
CADD	9.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0579% East Asian · 26/44,890 alleles

Filtering AF 0.0405% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0347%

Overall 0.0253% 408/1,614,210 alleles · ultra-rare exomes 380/1,461,886 · genomes 28/152,324 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0579%	1,727
South Asian	0.0384%	2,602
European (non-Finnish)	0.0274%	3,653
Finnishnot grpmax-eligible	0.0141%	7,117
Remaining individualsnot grpmax-eligible	0.0128%	7,814
African / African-American	0.00799%	12,508
Admixed American	0.00167%	60,026

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.Ser140=
Coding: c.420T>C
MANE Select: NM_005422
dbSNP: rs141090151
Type: single nucleotide variant
Location: chr11:121109432 (GRCh38)

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

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-ser140 (accessed [today's date]).

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