Is TECTA p.Arg284Cys (c.850C>T) pathogenic?

TECTA p.Arg284Cys (c.850C>T) is classified Uncertain significance in TECTA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-02-10). AlphaMissense: likely pathogenic (0.8125); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with TECTA p.Arg284Cys (c.850C>T)?

TECTA p.Arg284Cys (c.850C>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.Arg284Cys (c.850C>T) in the general population?

TECTA p.Arg284Cys (c.850C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about TECTA p.Arg284Cys (c.850C>T)?

AlphaMissense predicts likely pathogenic (score 0.8125) — an in-silico prediction, not a clinical call.

TECTA p.Arg284Cys

c.850C>T · rs1176214445 · VCV879126

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8125 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8125	likely pathogenic
REVEL	0.475	indeterminate
SaProt	LLR -9.67	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 66 kb · p 0.00019 · regional, not allelic
Overall
CADD	33.0	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00062% 10/1,614,110 alleles · ultra-rare exomes 10/1,461,848 · genomes 0/152,262 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00167%	60,020
European (non-Finnish)	0.000593%	168,575

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.Arg284Cys
Coding: c.850C>T
MANE Select: NM_005422
dbSNP: rs1176214445
Type: single nucleotide variant
Location: chr11:121118365 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.64
Residue 284: the vwfc domain; a UniProt-annotated variant site (in a breast cancer sample; somatic mutation)

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.Arg284His Uncertain significance ★ ⚠ same residue
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.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-arg284cys (accessed [today's date]).

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