Is TESK2 p.Pro40Ser (c.118C>T) pathogenic?

TESK2 p.Pro40Ser (c.118C>T) is classified Uncertain significance in TESK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.1682); Absent from gnomAD v4.1.

How common is TESK2 p.Pro40Ser (c.118C>T) in the general population?

TESK2 p.Pro40Ser (c.118C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TESK2 p.Pro40Ser (c.118C>T)?

AlphaMissense predicts likely benign (score 0.1682) — an in-silico prediction, not a clinical call.

TESK2 p.Pro40Ser

c.118C>T · rs757425136 · VCV3176178

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1682 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1682	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -4.26	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 3.5	GERP -1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 113 kb · p 0.0015 · regional, not allelic
Overall
CADD	14.8	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.

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: TESK2
Protein: p.Pro40Ser
Coding: c.118C>T
MANE Select: NM_007170
dbSNP: rs757425136
Type: single nucleotide variant
Location: chr1:45457668 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.52

Full TESK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TESK2 p.Arg455Cys Benign ★★ same type
TESK2 p.Ala393Thr Uncertain significance ★ ⚠ same type
TESK2 p.Ala394Gly Uncertain significance ★ ⚠ same type
TESK2 p.Ala509Thr Uncertain significance ★ ⚠ same type
TESK2 p.Ala512Thr Uncertain significance ★ ⚠ same type
TESK2 p.Ala79Gly Uncertain significance ★ ⚠ same type
TESK2 p.Arg18Cys Uncertain significance ★ ⚠ same type
TESK2 p.Arg18Gly Uncertain significance ★ ⚠ 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/tesk2-p-pro40ser (accessed [today's date]).

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