Is TELO2 p.Arg609His (c.1826G>A) pathogenic?

TELO2 p.Arg609His (c.1826G>A) is classified Pathogenic/Likely pathogenic in TELO2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-01-04). AlphaMissense: likely pathogenic (0.7147); Very rare (popmax 0.00267%, afr); Associated with TELO2-related intellectual disability-neurodevelopmental disorder.

What condition is associated with TELO2 p.Arg609His (c.1826G>A)?

TELO2 p.Arg609His (c.1826G>A) is associated with TELO2-related intellectual disability-neurodevelopmental disorder (ClinVar).

How common is TELO2 p.Arg609His (c.1826G>A) in the general population?

TELO2 p.Arg609His (c.1826G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about TELO2 p.Arg609His (c.1826G>A)?

AlphaMissense predicts likely pathogenic (score 0.7147) — an in-silico prediction, not a clinical call.

TELO2 p.Arg609His

c.1826G>A · rs754162070 · VCV236229

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7147 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

TELO2-related intellectual disability-neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.7147	likely pathogenic ✓ concordant with ClinVar · top 10% in TELO2
REVEL	0.553	indeterminate
SaProt	LLR -14.37	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	33.0	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 0.00267% African / African-American · 2/74,934 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000497% 8/1,610,742 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,467
Finnishnot grpmax-eligible	0.00165%	60,758
European (non-Finnish)	0.000424%	236,002

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.Arg609His
Coding: c.1826G>A
MANE Select: NM_016111
dbSNP: rs754162070
Type: single nucleotide variant
Location: chr16:1502986 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.74 · 4 PDB
Residue 609: 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 p.Arg609Cys Pathogenic ★ same residue
TELO2 p.Arg609Leu Uncertain significance ★ ⚠ same residue
TELO2 c.2034+2T>C Likely pathogenic ★★ same condition
TELO2 p.Arg403Ter 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

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-arg609his (accessed [today's date]).

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