Is TECTA p.Ile254= (c.762T>A) pathogenic?

TECTA p.Ile254= (c.762T>A) is classified Uncertain significance in TECTA (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0494%, afr); Associated with autosomal recessive nonsyndromic hearing loss 21.

What condition is associated with TECTA p.Ile254= (c.762T>A)?

TECTA p.Ile254= (c.762T>A) is associated with autosomal recessive nonsyndromic hearing loss 21, autosomal dominant nonsyndromic hearing loss 12 (ClinVar).

How common is TECTA p.Ile254= (c.762T>A) in the general population?

TECTA p.Ile254= (c.762T>A) is ultra-rare (popmax 0.0494%, afr) (gnomAD).

TECTA p.Ile254=

c.762T>A · rs142743467 · VCV302993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, afr)

Conditions

autosomal recessive nonsyndromic hearing loss 21

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 0.16	GERP 1.4, phastCons 0.99
Overall
CADD	7.231	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0494% African / African-American · 37/74,916 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0325%

Overall 0.00266% 43/1,613,752 alleles · ultra-rare exomes 26/1,461,614 · genomes 17/152,138 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0494%	2,025
Remaining individualsnot grpmax-eligible	0.008%	12,496
European (non-Finnish)	8.47e-05%	1,180,018

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.Ile254=
Coding: c.762T>A
MANE Select: NM_005422
dbSNP: rs142743467
Type: single nucleotide variant
Location: chr11:121113690 (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 recessive nonsyndromic hearing loss 21 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant nonsyndromic hearing loss 12

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-ile254 (accessed [today's date]).

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