Is TECTA p.Arg1186Trp (c.3556C>T) pathogenic?

TECTA p.Arg1186Trp (c.3556C>T) is classified Conflicting classifications of pathogenicity in TECTA (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-09-29). AlphaMissense: likely pathogenic (0.7007); Rare (popmax 0.576%, sas); Associated with autosomal recessive nonsyndromic hearing loss 21.

What condition is associated with TECTA p.Arg1186Trp (c.3556C>T)?

TECTA p.Arg1186Trp (c.3556C>T) is associated with autosomal recessive nonsyndromic hearing loss 21, autosomal dominant nonsyndromic hearing loss 12 (ClinVar).

How common is TECTA p.Arg1186Trp (c.3556C>T) in the general population?

TECTA p.Arg1186Trp (c.3556C>T) is rare (popmax 0.576%, sas) (gnomAD).

What do computational predictors say about TECTA p.Arg1186Trp (c.3556C>T)?

AlphaMissense predicts likely pathogenic (score 0.7007) — an in-silico prediction, not a clinical call.

TECTA p.Arg1186Trp

c.3556C>T · rs148098950 · VCV303016

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.7007 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.576%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal recessive nonsyndromic hearing loss 21

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.7007	likely pathogenic
REVEL	0.352	indeterminate
SaProt	LLR -8.89	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.7	GERP -0.12, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 66 kb · p 0.00019 · regional, not allelic
Overall
CADD	25.9	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 0.576% South Asian · 525/91,078 alleles

Filtering AF 0.536% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.519%

Overall 0.0519% 838/1,614,196 alleles · rare exomes 778/1,461,888 · genomes 60/152,308 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.576%	173
Middle Eastern	0.099%	1,010
Remaining individualsnot grpmax-eligible	0.0544%	1,839
Admixed American	0.035%	2,858
East Asian	0.0201%	4,987
European (non-Finnish)	0.0198%	5,043
African / African-American	0.012%	8,340

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.Arg1186Trp
Coding: c.3556C>T
MANE Select: NM_005422
dbSNP: rs148098950
Type: single nucleotide variant
Location: chr11:121145567 (GRCh38)

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

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-arg1186trp (accessed [today's date]).

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