Is TECTA p.Phe439Ser (c.1316T>C) pathogenic?

TECTA p.Phe439Ser (c.1316T>C) is classified Uncertain significance in TECTA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-19). AlphaMissense: likely pathogenic (0.951); Very rare (popmax 0.00266%, afr); Associated with autosomal dominant nonsyndromic hearing loss 12.

What condition is associated with TECTA p.Phe439Ser (c.1316T>C)?

TECTA p.Phe439Ser (c.1316T>C) is associated with autosomal dominant nonsyndromic hearing loss 12 (ClinVar).

How common is TECTA p.Phe439Ser (c.1316T>C) in the general population?

TECTA p.Phe439Ser (c.1316T>C) is very rare (popmax 0.00266%, afr) (gnomAD).

What do computational predictors say about TECTA p.Phe439Ser (c.1316T>C)?

AlphaMissense predicts likely pathogenic (score 0.951) — an in-silico prediction, not a clinical call.

TECTA p.Phe439Ser

c.1316T>C · rs1484775139 · VCV2441747

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.951 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00266%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal dominant nonsyndromic hearing loss 12

Computational evidence

Protein change
AlphaMissense	0.951	likely pathogenic
REVEL	0.335	indeterminate
SaProt	LLR -11.21	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP -0.78, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 66 kb · p 0.00019 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00266% African / African-American · 2/75,074 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,614,252 alleles · very rare exomes 2/1,461,874 · genomes 0/152,378 · joint denominator

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.Phe439Ser
Coding: c.1316T>C
MANE Select: NM_005422
dbSNP: rs1484775139
Type: single nucleotide variant
Location: chr11:121125414 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.64
Residue 439: the vwfd 1 domain

Full TECTA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant nonsyndromic hearing loss 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TECTA p.Arg371Gly Benign ★★★ same condition
TECTA c.4690-1G>A Pathogenic/Likely 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
TECTA p.Cys294Arg 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-phe439ser (accessed [today's date]).

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