Is TECTA p.Leu1777= (c.5331G>A) pathogenic?

TECTA p.Leu1777= (c.5331G>A) is classified Likely pathogenic in TECTA (ClinVar, Single submitter, 2 submitters; last evaluated 2025-02-25). Absent from gnomAD v4.1; Associated with autosomal dominant nonsyndromic hearing loss 12.

What condition is associated with TECTA p.Leu1777= (c.5331G>A)?

TECTA p.Leu1777= (c.5331G>A) is associated with autosomal dominant nonsyndromic hearing loss 12 (ClinVar).

How common is TECTA p.Leu1777= (c.5331G>A) in the general population?

TECTA p.Leu1777= (c.5331G>A) is absent from gnomAD v4.1 (gnomAD).

TECTA p.Leu1777=

c.5331G>A · rs1591462832 · VCV7024

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 2.5	GERP 0.67, phastCons 1
Overall
CADD	5.956	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TECTA
Protein: p.Leu1777=
Coding: c.5331G>A
MANE Select: NM_005422
dbSNP: rs1591462832
Type: single nucleotide variant
Location: chr11:121165331 (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

Similar variants

TECTA p.Arg371Gly Benign ★★★ same condition
TECTA c.4690-1G>A Pathogenic/Likely 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
TECTA p.Cys1402Ser Uncertain significance ★★ ⚠ same condition
TECTA p.Cys294Arg 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-leu1777 (accessed [today's date]).

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