Is TELO2 p.Pro164Ser (c.490C>T) pathogenic?

TELO2 p.Pro164Ser (c.490C>T) is classified Uncertain significance in TELO2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-15). AlphaMissense: likely pathogenic (0.8104); Very rare (popmax 0.0022%, sas); Associated with TELO2-related intellectual disability-neurodevelopmental disorder.

What condition is associated with TELO2 p.Pro164Ser (c.490C>T)?

TELO2 p.Pro164Ser (c.490C>T) is associated with TELO2-related intellectual disability-neurodevelopmental disorder (ClinVar).

How common is TELO2 p.Pro164Ser (c.490C>T) in the general population?

TELO2 p.Pro164Ser (c.490C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about TELO2 p.Pro164Ser (c.490C>T)?

AlphaMissense predicts likely pathogenic (score 0.8104) — an in-silico prediction, not a clinical call.

TELO2 p.Pro164Ser

c.490C>T · rs1463971276 · VCV2585502

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8104 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TELO2-related intellectual disability-neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.8104	likely pathogenic · top 6% in TELO2
REVEL	0.804	moderately pathogenic-leaning
SaProt	LLR -8.59	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,052 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000206% 3/1,458,578 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,526
Remaining individualsnot grpmax-eligible	0.0016%	62,462

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.Pro164Ser
Coding: c.490C>T
MANE Select: NM_016111
dbSNP: rs1463971276
Type: single nucleotide variant
Location: chr16:1495500 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.74 · 4 PDB

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

Disease context

TELO2-related intellectual disability-neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TELO2 c.2034+2T>C Likely pathogenic ★★ same condition
TELO2 p.Arg403Ter Pathogenic/Likely pathogenic ★★ same condition
TELO2 p.Arg609His Pathogenic/Likely pathogenic ★★ same condition
TELO2 p.Cys367Phe Pathogenic/Likely pathogenic ★★ same condition
TELO2 c.830+5G>T Uncertain significance ★★ same condition
TELO2 p.Ala323Pro Uncertain significance ★★ ⚠ same condition
TELO2 p.Arg377Trp Uncertain significance ★★ ⚠ same condition
TELO2 p.Arg516Trp 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/telo2-p-pro164ser (accessed [today's date]).

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