Is TECTA p.Val2026Ile (c.6076G>A) pathogenic?

TECTA p.Val2026Ile (c.6076G>A) is classified Conflicting classifications of pathogenicity in TECTA (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-18). AlphaMissense: likely benign (0.1658); Ultra-rare (popmax 0.0165%, sas); Associated with Inborn genetic diseases.

What condition is associated with TECTA p.Val2026Ile (c.6076G>A)?

TECTA p.Val2026Ile (c.6076G>A) is associated with Inborn genetic diseases, autosomal recessive nonsyndromic hearing loss 21 (ClinVar).

How common is TECTA p.Val2026Ile (c.6076G>A) in the general population?

TECTA p.Val2026Ile (c.6076G>A) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

What do computational predictors say about TECTA p.Val2026Ile (c.6076G>A)?

AlphaMissense predicts likely benign (score 0.1658) — an in-silico prediction, not a clinical call.

TECTA p.Val2026Ile

c.6076G>A · rs765995024 · VCV1806638

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1658 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1658	likely benign
REVEL	0.537	indeterminate
SaProt	LLR -7.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 20 kb · p 3.2e-06 · regional, not allelic
Overall
CADD	32.0	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% South Asian · 15/91,088 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00502% 81/1,614,104 alleles · ultra-rare exomes 71/1,461,890 · genomes 10/152,214 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,073
Middle Eastern	0.0164%	6,084
European (non-Finnish)	0.00492%	20,346
East Asian	0.00445%	22,451
African / African-American	0.004%	24,979
Admixed American	0.00333%	29,999

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.Val2026Ile
Coding: c.6076G>A
MANE Select: NM_005422
dbSNP: rs765995024
Type: single nucleotide variant
Location: chr11:121187908 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.64
Residue 2026: the zp domain

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 recessive nonsyndromic hearing loss 21

Similar variants

TECTA p.Arg371Gly Benign ★★★ same condition
TECTA c.2367+2T>C 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
TECTA p.Cys1402Ser 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-val2026ile (accessed [today's date]).

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