Is TECTA p.Asp725= (c.2175C>T) pathogenic?

TECTA p.Asp725= (c.2175C>T) is classified Uncertain significance in TECTA (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.033%, mid); Associated with autosomal dominant nonsyndromic hearing loss 12.

What condition is associated with TECTA p.Asp725= (c.2175C>T)?

TECTA p.Asp725= (c.2175C>T) is associated with autosomal dominant nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 21 (ClinVar).

How common is TECTA p.Asp725= (c.2175C>T) in the general population?

TECTA p.Asp725= (c.2175C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

TECTA p.Asp725=

c.2175C>T · rs865971914 · VCV878627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -12	GERP -3.6
Overall
CADD	1.988	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000124% 2/1,611,944 alleles · ultra-rare exomes 2/1,459,594 · genomes 0/152,350 · joint denominator

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.Asp725=
Coding: c.2175C>T
MANE Select: NM_005422
dbSNP: rs865971914
Type: single nucleotide variant
Location: chr11:121128152 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.64
Residue 725: the vwfd 2 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

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-asp725 (accessed [today's date]).

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