Is TELO2 p.Arg254Ser (c.760C>A) pathogenic?

TELO2 p.Arg254Ser (c.760C>A) is classified Uncertain significance in TELO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: ambiguous (0.4139); Very rare (popmax 0.0019%, amr); Associated with Inborn genetic diseases.

What condition is associated with TELO2 p.Arg254Ser (c.760C>A)?

TELO2 p.Arg254Ser (c.760C>A) is associated with Inborn genetic diseases (ClinVar).

How common is TELO2 p.Arg254Ser (c.760C>A) in the general population?

TELO2 p.Arg254Ser (c.760C>A) is very rare (popmax 0.0019%, amr) (gnomAD).

What do computational predictors say about TELO2 p.Arg254Ser (c.760C>A)?

AlphaMissense predicts ambiguous (score 0.4139) — an in-silico prediction, not a clinical call.

TELO2 p.Arg254Ser

c.760C>A · rs374512269 · VCV2616149

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4139 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0019%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4139	ambiguous
REVEL	0.551	indeterminate
SaProt	LLR -5.21	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.34, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	23.6	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 0.0019% Admixed American · 1/52,760 alleles

Overall 0.000128% 2/1,564,628 alleles · very rare exomes 2/1,412,288 · genomes 0/152,340 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0019%	52,760
European (non-Finnish)	8.65e-05%	1,155,759

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.Arg254Ser
Coding: c.760C>A
MANE Select: NM_016111
dbSNP: rs374512269
Type: single nucleotide variant
Location: chr16:1497438 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.74 · 4 PDB
Residue 254: an α-helix

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.Arg254Cys Uncertain significance ★ ⚠ same residue
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

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-arg254ser (accessed [today's date]).

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