Is TEX14 p.Ser355Pro (c.1063T>C) pathogenic?

TEX14 p.Ser355Pro (c.1063T>C) is classified Uncertain significance in TEX14 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). AlphaMissense: likely pathogenic (0.7749); Absent from gnomAD v4.1.

How common is TEX14 p.Ser355Pro (c.1063T>C) in the general population?

TEX14 p.Ser355Pro (c.1063T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TEX14 p.Ser355Pro (c.1063T>C)?

AlphaMissense predicts likely pathogenic (score 0.7749) — an in-silico prediction, not a clinical call.

TEX14 p.Ser355Pro

c.1063T>C · rs2509554536 · VCV3176277

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7749 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7749	likely pathogenic · top 6% in TEX14
REVEL	0.599	indeterminate
SaProt	LLR -13.22	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.16, phastCons 0.63
Regional constraint	o/e 1.16	unconstrained · MANE · 50 kb · p 3.6e-05 · regional, not allelic
Overall
CADD	21.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S361P vs ClinVar S355P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TEX14
Protein: p.Ser355Pro
Coding: c.1063T>C
MANE Select: NM_031272
dbSNP: rs2509554536
Type: single nucleotide variant
Location: chr17:58611282 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.95 · 2 PDB
Residue 361 UniProt numbering: the protein kinase domain

Full TEX14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TEX14 p.Glu1351Gly Uncertain significance ★★ ⚠ same type
TEX14 c.2789-7T>C Benign ★★ same type
TEX14 c.3717+7A>G Likely benign ★★ same type
TEX14 p.Leu1380Phe Benign/Likely benign ★★ same type
TEX14 p.Thr979= Benign ★★ same type
TEX14 c.4267+1G>A Likely pathogenic ★ same type
TEX14 p.Arg1218Ter Likely pathogenic ★ same type
TEX14 p.Cys1183Ter Pathogenic ★ same type

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/tex14-p-ser355pro (accessed [today's date]).

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