Is TELO2 p.Val583Ile (c.1747G>A) pathogenic?

TELO2 p.Val583Ile (c.1747G>A) is classified Uncertain significance in TELO2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-11). AlphaMissense: likely benign (0.1026); Ultra-rare (popmax 0.0845%, sas); Associated with TELO2-related intellectual disability-neurodevelopmental disorder.

What condition is associated with TELO2 p.Val583Ile (c.1747G>A)?

TELO2 p.Val583Ile (c.1747G>A) is associated with TELO2-related intellectual disability-neurodevelopmental disorder (ClinVar).

How common is TELO2 p.Val583Ile (c.1747G>A) in the general population?

TELO2 p.Val583Ile (c.1747G>A) is ultra-rare (popmax 0.0845%, sas) (gnomAD).

What do computational predictors say about TELO2 p.Val583Ile (c.1747G>A)?

AlphaMissense predicts likely benign (score 0.1026) — an in-silico prediction, not a clinical call.

TELO2 p.Val583Ile

c.1747G>A · rs775272837 · VCV1676226

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1026 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0845%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TELO2-related intellectual disability-neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.1026	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -9.98	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 0.74	GERP 1.1, phastCons 0.14
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	16.86	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 0.0845% South Asian · 77/91,086 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0637%

Overall 0.00614% 99/1,612,272 alleles · ultra-rare exomes 90/1,459,930 · genomes 9/152,342 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0845%	1,183
Middle Eastern	0.0165%	6,058
African / African-American	0.0133%	7,504
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.000848%	117,985

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.Val583Ile
Coding: c.1747G>A
MANE Select: NM_016111
dbSNP: rs775272837
Type: single nucleotide variant
Location: chr16:1502738 (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-val583ile (accessed [today's date]).

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