Is TEX14 p.Ser689Pro (c.2065T>C) pathogenic?

TEX14 p.Ser689Pro (c.2065T>C) is classified Uncertain significance in TEX14 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-02). AlphaMissense: likely benign (0.1064); Very rare (popmax 0.00133%, afr).

How common is TEX14 p.Ser689Pro (c.2065T>C) in the general population?

TEX14 p.Ser689Pro (c.2065T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about TEX14 p.Ser689Pro (c.2065T>C)?

AlphaMissense predicts likely benign (score 0.1064) — an in-silico prediction, not a clinical call.

TEX14 p.Ser689Pro

c.2065T>C · rs1286599533 · VCV2305133

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1064 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1064	likely benign
REVEL	0.422	indeterminate
SaProt	LLR -8.04	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.3	GERP -1.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 45 kb · p 6e-05 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 S695P vs ClinVar S689P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,912 alleles

Overall 6.2e-05% 1/1,613,388 alleles · very rare exomes 0/1,461,250 · genomes 1/152,138 · 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: TEX14
Protein: p.Ser689Pro
Coding: c.2065T>C
MANE Select: NM_031272
dbSNP: rs1286599533
Type: single nucleotide variant
Location: chr17:58599280 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.95 · 2 PDB

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-ser689pro (accessed [today's date]).

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