Is TELO2 p.Asp720Val (c.2159A>T) pathogenic?

TELO2 p.Asp720Val (c.2159A>T) is classified Conflicting classifications of pathogenicity in TELO2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2018-08-17). AlphaMissense: likely pathogenic (0.9026); Very rare (popmax 0.00432%, nfe); Associated with TELO2-related intellectual disability-neurodevelopmental disorder.

What condition is associated with TELO2 p.Asp720Val (c.2159A>T)?

TELO2 p.Asp720Val (c.2159A>T) is associated with TELO2-related intellectual disability-neurodevelopmental disorder (ClinVar).

How common is TELO2 p.Asp720Val (c.2159A>T) in the general population?

TELO2 p.Asp720Val (c.2159A>T) is very rare (popmax 0.00432%, nfe) (gnomAD).

What do computational predictors say about TELO2 p.Asp720Val (c.2159A>T)?

AlphaMissense predicts likely pathogenic (score 0.9026) — an in-silico prediction, not a clinical call.

TELO2 p.Asp720Val

c.2159A>T · rs878853271 · VCV236226

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9026 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00432%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TELO2-related intellectual disability-neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.9026	likely pathogenic · top 3% in TELO2
REVEL	0.756	pathogenic-leaning
SaProt	LLR -13.46	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	28.2	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 0.00432% European (non-Finnish) · 51/1,179,280 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00335% 54/1,612,030 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00432%	23,123
Remaining individualsnot grpmax-eligible	0.00321%	31,199
African / African-American	0.00134%	74,876

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.Asp720Val
Coding: c.2159A>T
MANE Select: NM_016111
dbSNP: rs878853271
Type: single nucleotide variant
Location: chr16:1506984 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.74 · 4 PDB
Residue 720: a UniProt-annotated variant site (in yhfs)

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-asp720val (accessed [today's date]).

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