Is TELO2 p.Ala805= (c.2415T>C) pathogenic?

TELO2 p.Ala805= (c.2415T>C) is classified Benign in TELO2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). Common (popmax 64.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with TELO2-related intellectual disability-neurodevelopmental disorder.

What condition is associated with TELO2 p.Ala805= (c.2415T>C)?

TELO2 p.Ala805= (c.2415T>C) is associated with TELO2-related intellectual disability-neurodevelopmental disorder (ClinVar).

TELO2 p.Ala805=

Q: How common is TELO2 p.Ala805= (c.2415T>C) in the general population?

TELO2 p.Ala805= (c.2415T>C) is common (popmax 64.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2415T>C · rs3180228 · VCV1185498

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 64.2%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

TELO2-related intellectual disability-neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -4.6
Overall
CADD	0.012	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 64.2% African / African-American · 48,067/74,920 alleles

Filtering AF 63.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 63.5%

Overall 28% 451,043/1,610,186 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	64.2%	2
East Asian	41.6%	2
South Asian	39%	3
Middle Eastern	36.9%	3
Remaining individualsnot grpmax-eligible	30.8%	3
Ashkenazi Jewishnot grpmax-eligible	28.7%	3
Finnishnot grpmax-eligible	25.7%	4
European (non-Finnish)	24.8%	4
Amishnot grpmax-eligible	20.4%	5
Admixed American	18.3%	5

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.Ala805=
Coding: c.2415T>C
MANE Select: NM_016111
dbSNP: rs3180228
Type: single nucleotide variant
Location: chr16:1509837 (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-ala805 (accessed [today's date]).

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