Is TECTA p.Ala495= (c.1485A>G) pathogenic?

TECTA p.Ala495= (c.1485A>G) is classified Benign in TECTA (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 93.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive nonsyndromic hearing loss 21.

What condition is associated with TECTA p.Ala495= (c.1485A>G)?

TECTA p.Ala495= (c.1485A>G) is associated with autosomal recessive nonsyndromic hearing loss 21, autosomal dominant nonsyndromic hearing loss 12 (ClinVar).

TECTA p.Ala495=

Q: How common is TECTA p.Ala495= (c.1485A>G) in the general population?

TECTA p.Ala495= (c.1485A>G) is common (popmax 93.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1485A>G · rs536069 · VCV45315

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 93.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

autosomal recessive nonsyndromic hearing loss 21

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 -16	GERP -3.6
Overall
CADD	0.034	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 93.4% African / African-American · 70,102/75,030 alleles

Filtering AF 92.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 92.6%

Overall 70.8% 1,142,468/1,613,962 alleles · common exomes 1,027,389/1,461,720 · genomes 115,079/152,242 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	93.4%	1
Finnishnot grpmax-eligible	73.4%	1
South Asian	72.2%	1
Remaining individualsnot grpmax-eligible	71%	1
Middle Eastern	70.5%	1
European (non-Finnish)	69.8%	1
East Asian	68.1%	1
Admixed American	63.5%	2
Amishnot grpmax-eligible	62.4%	2
Ashkenazi Jewishnot grpmax-eligible	62.1%	2

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.Ala495=
Coding: c.1485A>G
MANE Select: NM_005422
dbSNP: rs536069
Type: single nucleotide variant
Location: chr11:121125583 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.64
Residue 495: the vwfd 1 domain

Full TECTA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive nonsyndromic hearing loss 21 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant nonsyndromic hearing loss 12

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-ala495 (accessed [today's date]).

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