Is TELO2 p.Pro5Arg (c.14C>G) pathogenic?

TELO2 p.Pro5Arg (c.14C>G) is classified Conflicting classifications of pathogenicity in TELO2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-08). AlphaMissense: likely benign (0.069); Ultra-rare (popmax 0.0653%, afr); Associated with Inborn genetic diseases.

What condition is associated with TELO2 p.Pro5Arg (c.14C>G)?

TELO2 p.Pro5Arg (c.14C>G) is associated with Inborn genetic diseases (ClinVar).

How common is TELO2 p.Pro5Arg (c.14C>G) in the general population?

TELO2 p.Pro5Arg (c.14C>G) is ultra-rare (popmax 0.0653%, afr) (gnomAD).

What do computational predictors say about TELO2 p.Pro5Arg (c.14C>G)?

AlphaMissense predicts likely benign (score 0.069) — an in-silico prediction, not a clinical call.

TELO2 p.Pro5Arg

c.14C>G · rs61742313 · VCV2525406

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.069 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0653%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.069	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -10.49	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.2	GERP -4.2
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	0.002	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 0.0653% African / African-American · 49/75,016 alleles

Filtering AF 0.0507% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0455%

Overall 0.00353% 57/1,612,936 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0653%	1,531
Remaining individualsnot grpmax-eligible	0.008%	12,497
Admixed American	0.00167%	60,008
European (non-Finnish)	0.00017%	589,835

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.Pro5Arg
Coding: c.14C>G
MANE Select: NM_016111
dbSNP: rs61742313
Type: single nucleotide variant
Location: chr16:1494295 (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-pro5arg (accessed [today's date]).

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