Is TECTA p.Phe1511= (c.4533C>T) pathogenic?

TECTA p.Phe1511= (c.4533C>T) is classified Conflicting classifications of pathogenicity in TECTA (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-27). Low-frequency (popmax 3.61%, afr); Associated with autosomal recessive nonsyndromic hearing loss 21.

What condition is associated with TECTA p.Phe1511= (c.4533C>T)?

TECTA p.Phe1511= (c.4533C>T) is associated with autosomal recessive nonsyndromic hearing loss 21, autosomal dominant nonsyndromic hearing loss 12 (ClinVar).

How common is TECTA p.Phe1511= (c.4533C>T) in the general population?

TECTA p.Phe1511= (c.4533C>T) is low-frequency (popmax 3.61%, afr) (gnomAD).

TECTA p.Phe1511=

c.4533C>T · rs77628498 · VCV45332

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.61%, afr)

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 -1.1	GERP -1.2, phastCons 0.001
Overall
CADD	9.762	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.61% African / African-American · 2,708/75,064 alleles

Filtering AF 3.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.45%

Overall 0.183% 2,955/1,613,884 alleles · low-frequency exomes 1,404/1,461,520 · genomes 1,551/152,364 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.61%	28
Remaining individualsnot grpmax-eligible	0.211%	474
Admixed American	0.147%	682
Middle Eastern	0.099%	1,010
South Asian	0.00768%	13,013
European (non-Finnish)	0.00119%	84,286

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.Phe1511=
Coding: c.4533C>T
MANE Select: NM_005422
dbSNP: rs77628498
Type: single nucleotide variant
Location: chr11:121158068 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.64
Residue 1511: the vwfd 4 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-phe1511 (accessed [today's date]).

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