Is TECTA p.Ser1878= (c.5634C>T) pathogenic?

TECTA p.Ser1878= (c.5634C>T) is classified Benign in TECTA (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-01). Common (popmax 31.4%, sas) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive nonsyndromic hearing loss 21.

What condition is associated with TECTA p.Ser1878= (c.5634C>T)?

TECTA p.Ser1878= (c.5634C>T) is associated with autosomal recessive nonsyndromic hearing loss 21, autosomal dominant nonsyndromic hearing loss 12 (ClinVar).

TECTA p.Ser1878=

Q: How common is TECTA p.Ser1878= (c.5634C>T) in the general population?

TECTA p.Ser1878= (c.5634C>T) is common (popmax 31.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5634C>T · rs2155369 · VCV45338

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 31.4%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

autosomal recessive nonsyndromic hearing loss 21

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -1.7, phastCons 0.003
Overall
CADD	8.497	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 31.4% South Asian · 28,588/91,072 alleles

Filtering AF 31.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 31%

Overall 13.9% 224,852/1,613,960 alleles · common exomes 206,629/1,461,774 · genomes 18,223/152,186 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	31.4%	3
East Asian	29.2%	3
Middle Eastern	23.3%	4
Amishnot grpmax-eligible	19.8%	5
Admixed American	19.7%	5
Remaining individualsnot grpmax-eligible	16.1%	6
Ashkenazi Jewishnot grpmax-eligible	15.8%	6
European (non-Finnish)	12.3%	8
Finnishnot grpmax-eligible	11.2%	9
African / African-American	2.99%	33

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.Ser1878=
Coding: c.5634C>T
MANE Select: NM_005422
dbSNP: rs2155369
Type: single nucleotide variant
Location: chr11:121168101 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.64
Residue 1878: the zp 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-ser1878 (accessed [today's date]).

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