Is TECTA p.Ser1584Thr (c.4751G>C) pathogenic?

TECTA p.Ser1584Thr (c.4751G>C) is classified Benign/Likely benign in TECTA (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0799); Common (popmax 7.15%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive nonsyndromic hearing loss 21.

What condition is associated with TECTA p.Ser1584Thr (c.4751G>C)?

TECTA p.Ser1584Thr (c.4751G>C) is associated with autosomal recessive nonsyndromic hearing loss 21, autosomal dominant nonsyndromic hearing loss 12 (ClinVar).

What do computational predictors say about TECTA p.Ser1584Thr (c.4751G>C)?

AlphaMissense predicts likely benign (score 0.0799) — an in-silico prediction, not a clinical call.

TECTA p.Ser1584Thr

Q: How common is TECTA p.Ser1584Thr (c.4751G>C) in the general population?

TECTA p.Ser1584Thr (c.4751G>C) is common (popmax 7.15%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4751G>C · rs34963131 · VCV45334

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0799 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.15%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive nonsyndromic hearing loss 21

Computational evidence

Protein change
AlphaMissense	0.0799	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -7.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 0.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 66 kb · p 0.00019 · regional, not allelic
Overall
CADD	18.81	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 7.15% African / African-American · 5,364/75,000 alleles

Filtering AF 6.99% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.93%

Overall 0.378% 6,109/1,614,140 alleles · common exomes 3,122/1,461,892 · genomes 2,987/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.15%	14
Remaining individualsnot grpmax-eligible	0.474%	211
Admixed American	0.436%	229
Middle Eastern	0.247%	404
European (non-Finnish)	0.0136%	7,375
South Asian	0.0132%	7,589

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.Ser1584Thr
Coding: c.4751G>C
MANE Select: NM_005422
dbSNP: rs34963131
Type: single nucleotide variant
Location: chr11:121160196 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.64
Residue 1584: the vwfd 4 domain; a UniProt-annotated variant site (in)

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.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-ser1584thr (accessed [today's date]).

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