Is TECTA p.Ser1847Pro (c.5539T>C) pathogenic?

TECTA p.Ser1847Pro (c.5539T>C) is classified Likely pathogenic in TECTA (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-28). AlphaMissense: likely pathogenic (0.9949); Absent from gnomAD v4.1; Associated with autosomal dominant nonsyndromic hearing loss 12.

What condition is associated with TECTA p.Ser1847Pro (c.5539T>C)?

TECTA p.Ser1847Pro (c.5539T>C) is associated with autosomal dominant nonsyndromic hearing loss 12 (ClinVar).

How common is TECTA p.Ser1847Pro (c.5539T>C) in the general population?

TECTA p.Ser1847Pro (c.5539T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TECTA p.Ser1847Pro (c.5539T>C)?

AlphaMissense predicts likely pathogenic (score 0.9949) — an in-silico prediction, not a clinical call.

TECTA p.Ser1847Pro

c.5539T>C · rs1947057220 · VCV869465

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9949 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant nonsyndromic hearing loss 12

Computational evidence

Protein change
AlphaMissense	0.9949	likely pathogenic ✓ concordant with ClinVar · top 5% in TECTA
REVEL	0.724	pathogenic-leaning
SaProt	LLR -12.77	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 66 kb · p 0.00019 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

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.Ser1847Pro
Coding: c.5539T>C
MANE Select: NM_005422
dbSNP: rs1947057220
Type: single nucleotide variant
Location: chr11:121166733 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.64
Residue 1847: the zp domain

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-ser1847pro (accessed [today's date]).

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