Is TELO2 p.Arg403Ter (c.1207C>T) pathogenic?

TELO2 p.Arg403Ter (c.1207C>T) is classified Pathogenic/Likely pathogenic in TELO2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-13). Very rare (popmax 0.00333%, amr); Associated with TELO2-related intellectual disability-neurodevelopmental disorder.

What condition is associated with TELO2 p.Arg403Ter (c.1207C>T)?

TELO2 p.Arg403Ter (c.1207C>T) is associated with TELO2-related intellectual disability-neurodevelopmental disorder (ClinVar).

How common is TELO2 p.Arg403Ter (c.1207C>T) in the general population?

TELO2 p.Arg403Ter (c.1207C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

TELO2 p.Arg403Ter

c.1207C>T · rs572431474 · VCV1927535

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

TELO2-related intellectual disability-neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 21
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,994 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.00093% 15/1,612,392 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,997
South Asian	0.0022%	45,518
Remaining individualsnot grpmax-eligible	0.0016%	62,454
European (non-Finnish)	0.000848%	117,977

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.Arg403Ter
Coding: c.1207C>T
MANE Select: NM_016111
dbSNP: rs572431474
Type: single nucleotide variant
Location: chr16:1500625 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.74 · 4 PDB
Residue 403: an α-helix

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.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
TELO2 p.Arg668Gln 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-arg403ter (accessed [today's date]).

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