Is TECTA p.Asp505His (c.1513G>C) pathogenic?

TECTA p.Asp505His (c.1513G>C) is classified Uncertain significance in TECTA (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.2514); Absent from gnomAD v4.1; Associated with autosomal dominant nonsyndromic hearing loss 12.

What condition is associated with TECTA p.Asp505His (c.1513G>C)?

TECTA p.Asp505His (c.1513G>C) is associated with autosomal dominant nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 21 (ClinVar).

How common is TECTA p.Asp505His (c.1513G>C) in the general population?

TECTA p.Asp505His (c.1513G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TECTA p.Asp505His (c.1513G>C)?

AlphaMissense predicts likely benign (score 0.2514) — an in-silico prediction, not a clinical call.

TECTA p.Asp505His

c.1513G>C · VCV3381948

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2514 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant nonsyndromic hearing loss 12

Computational evidence

Protein change
AlphaMissense	0.2514	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -8.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 66 kb · p 0.00019 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Asp505His
Coding: c.1513G>C
MANE Select: NM_005422
Type: single nucleotide variant
Location: chr11:121125611 (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.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-asp505his (accessed [today's date]).

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