Is TELO2 p.Cys367Phe (c.1100G>T) pathogenic?

TELO2 p.Cys367Phe (c.1100G>T) is classified Pathogenic/Likely pathogenic in TELO2 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-01-05). AlphaMissense: ambiguous (0.5066); Ultra-rare (popmax 0.052%, amr); Associated with TELO2-related intellectual disability-neurodevelopmental disorder.

What condition is associated with TELO2 p.Cys367Phe (c.1100G>T)?

TELO2 p.Cys367Phe (c.1100G>T) is associated with TELO2-related intellectual disability-neurodevelopmental disorder (ClinVar).

How common is TELO2 p.Cys367Phe (c.1100G>T) in the general population?

TELO2 p.Cys367Phe (c.1100G>T) is ultra-rare (popmax 0.052%, amr) (gnomAD).

What do computational predictors say about TELO2 p.Cys367Phe (c.1100G>T)?

AlphaMissense predicts ambiguous (score 0.5066) — an in-silico prediction, not a clinical call.

TELO2 p.Cys367Phe

c.1100G>T · rs202020308 · VCV236225

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

AlphaMissense

ambiguous

0.5066 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.052%, amr)

Conditions

TELO2-related intellectual disability-neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.5066	ambiguous
REVEL	0.372	indeterminate
SaProt	LLR -11.56	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	25.0	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 0.052% Admixed American · 31/59,610 alleles

Filtering AF 0.0376% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0327%

Overall 0.0181% 291/1,609,910 alleles · ultra-rare exomes 265/1,457,534 · genomes 26/152,376 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.052%	1,923
European (non-Finnish)	0.0215%	4,661
Remaining individualsnot grpmax-eligible	0.00803%	12,455
African / African-American	0.00266%	37,526

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.Cys367Phe
Coding: c.1100G>T
MANE Select: NM_016111
dbSNP: rs202020308
Type: single nucleotide variant
Location: chr16:1500444 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.74 · 4 PDB
Residue 367: a UniProt-annotated variant site (in yhfs); 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.Arg403Ter Pathogenic/Likely pathogenic ★★ same condition
TELO2 p.Arg609His 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-cys367phe (accessed [today's date]).

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