Is TECTA p.Ala1046= (c.3138C>T) pathogenic?

TECTA p.Ala1046= (c.3138C>T) is classified Conflicting classifications of pathogenicity in TECTA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-12-05). Very rare (popmax 0.00136%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 21.

What condition is associated with TECTA p.Ala1046= (c.3138C>T)?

TECTA p.Ala1046= (c.3138C>T) is associated with autosomal recessive nonsyndromic hearing loss 21, autosomal dominant nonsyndromic hearing loss 12 (ClinVar).

How common is TECTA p.Ala1046= (c.3138C>T) in the general population?

TECTA p.Ala1046= (c.3138C>T) is very rare (popmax 0.00136%, nfe) (gnomAD).

TECTA p.Ala1046=

c.3138C>T · rs886047840 · VCV303013

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

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 2.2	GERP 0.54, phastCons 1
Overall
CADD	9.245	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,180,028 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00112% 18/1,613,894 alleles · very rare exomes 17/1,461,872 · genomes 1/152,022 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00136%	73,752
African / African-American	0.00134%	74,874
South Asian	0.0011%	91,080

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.Ala1046=
Coding: c.3138C>T
MANE Select: NM_005422
dbSNP: rs886047840
Type: single nucleotide variant
Location: chr11:121137617 (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-ala1046 (accessed [today's date]).

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