Is TERT p.Arg671Pro (c.2012G>C) pathogenic?

TERT p.Arg671Pro (c.2012G>C) is classified Uncertain significance in TERT (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-18). AlphaMissense: ambiguous (0.4996); Absent from gnomAD v4.1.

How common is TERT p.Arg671Pro (c.2012G>C) in the general population?

TERT p.Arg671Pro (c.2012G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TERT p.Arg671Pro (c.2012G>C)?

AlphaMissense predicts ambiguous (score 0.4996) — an in-silico prediction, not a clinical call.

TERT p.Arg671Pro

c.2012G>C · rs774381540 · VCV1337559

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4996	ambiguous
REVEL	0.505	indeterminate
SaProt	LLR -13.39	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -2.5
Regional constraint	o/e 0.58	unconstrained · MANE · 29 kb · p 2.3e-32 · regional, not allelic
Overall
CADD	12.52	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

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.Arg671Pro
Coding: c.2012G>C
MANE Select: NM_198253
dbSNP: rs774381540
Type: single nucleotide variant
Location: chr5:1279409 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 671: the reverse transcriptase domain; an α-helix

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

Similar variants

TERT p.Arg671Trp Pathogenic/Likely pathogenic ★★ ⚠ same residue
TERT p.Arg671= Likely benign ★★ same residue
TERT p.Arg671Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
TERT p.Arg671Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
TERT c.2130+1G>A Likely pathogenic ★★ same type
TERT c.2130+2T>G Likely pathogenic ★★ same type
TERT c.2131-2A>G Likely pathogenic ★★ same type
TERT c.2286+1G>A Likely pathogenic ★★ 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/tert-p-arg671pro (accessed [today's date]).

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