Is TECTA p.Ala1735= (c.5205C>T) pathogenic?

TECTA p.Ala1735= (c.5205C>T) is classified Conflicting classifications of pathogenicity in TECTA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-02-11). Ultra-rare (popmax 0.0824%, eas); Associated with autosomal dominant nonsyndromic hearing loss 12.

What condition is associated with TECTA p.Ala1735= (c.5205C>T)?

TECTA p.Ala1735= (c.5205C>T) is associated with autosomal dominant nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 21 (ClinVar).

How common is TECTA p.Ala1735= (c.5205C>T) in the general population?

TECTA p.Ala1735= (c.5205C>T) is ultra-rare (popmax 0.0824%, eas) (gnomAD).

TECTA p.Ala1735=

c.5205C>T · rs762504147 · VCV879785

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0824%, eas)

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 -20	GERP -3.4
Overall
CADD	0.863	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0824% East Asian · 37/44,904 alleles

Filtering AF 0.0614% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.00304% 49/1,613,286 alleles · ultra-rare exomes 48/1,461,010 · genomes 1/152,276 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0824%	1,214
Admixed American	0.0117%	8,574
Remaining individualsnot grpmax-eligible	0.0032%	31,236
South Asian	0.0011%	91,084
European (non-Finnish)	0.000169%	590,026

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.Ala1735=
Coding: c.5205C>T
MANE Select: NM_005422
dbSNP: rs762504147
Type: single nucleotide variant
Location: chr11:121162303 (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-ala1735 (accessed [today's date]).

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