Is TELO2 p.Ala750Pro (c.2248G>C) pathogenic?

TELO2 p.Ala750Pro (c.2248G>C) is classified Uncertain significance in TELO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-16). AlphaMissense: likely pathogenic (0.7006); Ultra-rare (popmax 0.0319%, sas); Associated with Inborn genetic diseases.

What condition is associated with TELO2 p.Ala750Pro (c.2248G>C)?

TELO2 p.Ala750Pro (c.2248G>C) is associated with Inborn genetic diseases (ClinVar).

How common is TELO2 p.Ala750Pro (c.2248G>C) in the general population?

TELO2 p.Ala750Pro (c.2248G>C) is ultra-rare (popmax 0.0319%, sas) (gnomAD).

What do computational predictors say about TELO2 p.Ala750Pro (c.2248G>C)?

AlphaMissense predicts likely pathogenic (score 0.7006) — an in-silico prediction, not a clinical call.

TELO2 p.Ala750Pro

c.2248G>C · VCV3325290

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7006 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0319%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7006	likely pathogenic
REVEL	0.237	benign-leaning
SaProt	LLR -10.77	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	25.9	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 0.0319% South Asian · 29/91,034 alleles

Filtering AF 0.0228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0196%

Overall 0.0018% 29/1,610,406 alleles · ultra-rare exomes 29/1,458,072 · genomes 0/152,334 · joint denominator

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.Ala750Pro
Coding: c.2248G>C
MANE Select: NM_016111
Type: single nucleotide variant
Location: chr16:1507327 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TELO2 p.Ala198Val Uncertain significance ★★ ⚠ same condition
TELO2 p.Ala511Ser Uncertain significance ★★ ⚠ same condition
TELO2 p.Ala658Val Uncertain significance ★★ ⚠ same condition
TELO2 p.Ala744Thr Uncertain significance ★★ ⚠ same condition
TELO2 p.Arg122Trp Uncertain significance ★★ ⚠ same condition
TELO2 p.Arg129Cys Uncertain significance ★★ ⚠ same condition
TELO2 p.Arg194Trp Uncertain significance ★★ ⚠ same condition
TELO2 p.Arg309Gln 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-ala750pro (accessed [today's date]).

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