Is TECTA p.Ser362Ile (c.1085G>T) pathogenic?

TECTA p.Ser362Ile (c.1085G>T) is classified Conflicting classifications of pathogenicity in TECTA (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-10-01). AlphaMissense: ambiguous (0.4764); Rare (popmax 0.324%, afr); Associated with Inborn genetic diseases.

What condition is associated with TECTA p.Ser362Ile (c.1085G>T)?

TECTA p.Ser362Ile (c.1085G>T) is associated with Inborn genetic diseases, autosomal dominant nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 21 (ClinVar).

How common is TECTA p.Ser362Ile (c.1085G>T) in the general population?

TECTA p.Ser362Ile (c.1085G>T) is rare (popmax 0.324%, afr) (gnomAD).

What do computational predictors say about TECTA p.Ser362Ile (c.1085G>T)?

AlphaMissense predicts ambiguous (score 0.4764) — an in-silico prediction, not a clinical call.

TECTA p.Ser362Ile

c.1085G>T · rs149001418 · VCV178533

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

ambiguous

0.4764 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.324%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4764	ambiguous
REVEL	0.308	indeterminate
SaProt	LLR -11.58	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 66 kb · p 0.00019 · regional, not allelic
Overall
CADD	26.9	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

Grpmax group 0.324% African / African-American · 243/75,038 alleles

Filtering AF 0.29% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.277%

Overall 0.0159% 257/1,614,148 alleles · rare exomes 118/1,461,882 · genomes 139/152,266 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.324%	309
Remaining individualsnot grpmax-eligible	0.0112%	8,930
Admixed American	0.00333%	30,011
European (non-Finnish)	0.000424%	236,007

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.Ser362Ile
Coding: c.1085G>T
MANE Select: NM_005422
dbSNP: rs149001418
Type: single nucleotide variant
Location: chr11:121118600 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.64
Residue 362: the vwfd 1 domain; a UniProt-annotated variant site (in dfna12)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant nonsyndromic hearing loss 12 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-ser362ile (accessed [today's date]).

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