Is TELO2 p.Pro147Ser (c.439C>T) pathogenic?

TELO2 p.Pro147Ser (c.439C>T) is classified Uncertain significance in TELO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-05). AlphaMissense: likely benign (0.0912); Very rare (popmax 0.00017%, nfe).

How common is TELO2 p.Pro147Ser (c.439C>T) in the general population?

TELO2 p.Pro147Ser (c.439C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about TELO2 p.Pro147Ser (c.439C>T)?

AlphaMissense predicts likely benign (score 0.0912) — an in-silico prediction, not a clinical call.

TELO2 p.Pro147Ser

c.439C>T · rs2142456159 · VCV1714586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0912 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0912	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -8.70	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 1.8	GERP -1.3, phastCons 0.28
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	4.743	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

Grpmax group 0.00017% European (non-Finnish) · 2/1,177,920 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,606,610 alleles · very rare exomes 2/1,454,210 · genomes 0/152,400 · 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: TELO2
Protein: p.Pro147Ser
Coding: c.439C>T
MANE Select: NM_016111
dbSNP: rs2142456159
Type: single nucleotide variant
Location: chr16:1495449 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.74 · 4 PDB
Residue 147: an α-helix

Full TELO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TELO2 p.Pro147= Likely benign ★ same residue
TELO2 c.2034+2T>C Likely pathogenic ★★ same type
TELO2 c.2291+1G>C Likely pathogenic ★★ same type
TELO2 p.Arg403Ter Pathogenic/Likely pathogenic ★★ same type
TELO2 p.Arg609His Pathogenic/Likely pathogenic ★★ same type
TELO2 p.Cys367Phe Pathogenic/Likely pathogenic ★★ same type
TELO2 c.830+5G>T Uncertain significance ★★ same type
TELO2 p.Ala198Val 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/telo2-p-pro147ser (accessed [today's date]).

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