Is TECTA p.Arg284His (c.851G>A) pathogenic?

TECTA p.Arg284His (c.851G>A) is classified Uncertain significance in TECTA (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.1991); Very rare (popmax 0.00223%, eas); Associated with autosomal recessive nonsyndromic hearing loss 21.

What condition is associated with TECTA p.Arg284His (c.851G>A)?

TECTA p.Arg284His (c.851G>A) is associated with autosomal recessive nonsyndromic hearing loss 21, autosomal dominant nonsyndromic hearing loss 12 (ClinVar).

How common is TECTA p.Arg284His (c.851G>A) in the general population?

TECTA p.Arg284His (c.851G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about TECTA p.Arg284His (c.851G>A)?

AlphaMissense predicts likely benign (score 0.1991) — an in-silico prediction, not a clinical call.

TECTA p.Arg284His

c.851G>A · rs886047837 · VCV302994

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1991 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal recessive nonsyndromic hearing loss 21

Computational evidence

Protein change
AlphaMissense	0.1991	likely benign
REVEL	0.373	indeterminate
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 66 kb · p 0.00019 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,904 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000929% 15/1,613,990 alleles · very rare exomes 11/1,461,850 · genomes 4/152,140 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,904
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00133%	74,908
European (non-Finnish)	0.00102%	98,335

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.Arg284His
Coding: c.851G>A
MANE Select: NM_005422
dbSNP: rs886047837
Type: single nucleotide variant
Location: chr11:121118366 (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

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.Arg284Cys 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-arg284his (accessed [today's date]).

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