Is TERT p.Arg486Pro (c.1457G>C) pathogenic?

TERT p.Arg486Pro (c.1457G>C) is classified Uncertain significance in TERT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-27). AlphaMissense: likely pathogenic (0.8741); Absent from gnomAD v4.1; Associated with TERT-related disorder.

What condition is associated with TERT p.Arg486Pro (c.1457G>C)?

TERT p.Arg486Pro (c.1457G>C) is associated with TERT-related disorder (ClinVar).

How common is TERT p.Arg486Pro (c.1457G>C) in the general population?

TERT p.Arg486Pro (c.1457G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TERT p.Arg486Pro (c.1457G>C)?

AlphaMissense predicts likely pathogenic (score 0.8741) — an in-silico prediction, not a clinical call.

TERT p.Arg486Pro

c.1457G>C · rs1179486322 · VCV2630316

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8741 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TERT-related disorder

Computational evidence

Protein change
AlphaMissense	0.8741	likely pathogenic · top 8% in TERT
REVEL	0.647	pathogenic-leaning
SaProt	LLR -12.36	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 6.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 12 kb · p 0.082 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TERT
Protein: p.Arg486Pro
Coding: c.1457G>C
MANE Select: NM_198253
dbSNP: rs1179486322
Type: single nucleotide variant
Location: chr5:1293429 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 486: an α-helix; the 'required for oligomerization' region; the 'rna-interacting domain 2' region; the 'qfp motif' region

Full TERT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TERT-related disorder

Similar variants

TERT p.Arg486His Uncertain significance ★★ ⚠ same residue
TERT p.Arg486= Likely benign ★★ same residue
TERT p.Arg486Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
TERT p.Arg671Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
TERT p.Arg691Ser Uncertain significance ★★ ⚠ same condition
TERT p.Arg698Gln Uncertain significance ★★ ⚠ same condition
TERT p.Pro187Arg Uncertain significance ★★ ⚠ same condition
TERT p.Cys1015Ter Likely pathogenic ★ 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/tert-p-arg486pro (accessed [today's date]).

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