Is TELO2 p.Ala537Ser (c.1609G>T) pathogenic?

TELO2 p.Ala537Ser (c.1609G>T) is classified Uncertain significance in TELO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-15). AlphaMissense: likely benign (0.0929); No allele count reported in gnomAD v4.1 (AN 1,606,028).

How common is TELO2 p.Ala537Ser (c.1609G>T) in the general population?

TELO2 p.Ala537Ser (c.1609G>T) is no allele count reported in gnomAD v4.1 (AN 1,606,028) (gnomAD).

What do computational predictors say about TELO2 p.Ala537Ser (c.1609G>T)?

AlphaMissense predicts likely benign (score 0.0929) — an in-silico prediction, not a clinical call.

TELO2 p.Ala537Ser

c.1609G>T · rs2505963851 · VCV2101872

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0929 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,606,028)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0929	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -6.22	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 8.3	GERP 2.2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	21.3	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

No allele count reported in gnomAD v4.1 (AN 1,606,028). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TELO2
Protein: p.Ala537Ser
Coding: c.1609G>T
MANE Select: NM_016111
dbSNP: rs2505963851
Type: single nucleotide variant
Location: chr16:1502360 (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

Similar variants

TELO2 c.2034+2T>C Likely pathogenic ★★ same type
TELO2 c.2291+1G>C Likely pathogenic ★★ same type
TELO2 p.Arg403Ter Pathogenic/Likely pathogenic ★★ same type
TELO2 p.Arg609His Pathogenic/Likely pathogenic ★★ same type
TELO2 p.Cys367Phe Pathogenic/Likely pathogenic ★★ same type
TELO2 c.830+5G>T Uncertain significance ★★ same type
TELO2 p.Ala198Val Uncertain significance ★★ ⚠ same type
TELO2 p.Ala323Pro Uncertain significance ★★ ⚠ same type

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-ala537ser (accessed [today's date]).

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