Is TERT p.Arg248Pro (c.743G>C) pathogenic?

TERT p.Arg248Pro (c.743G>C) is classified Uncertain significance in TERT (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-27). AlphaMissense: likely benign (0.0757); Absent from gnomAD v4.1; Associated with idiopathic pulmonary fibrosis.

What condition is associated with TERT p.Arg248Pro (c.743G>C)?

TERT p.Arg248Pro (c.743G>C) is associated with idiopathic pulmonary fibrosis, dyskeratosis congenita, autosomal dominant 2 (ClinVar).

How common is TERT p.Arg248Pro (c.743G>C) in the general population?

TERT p.Arg248Pro (c.743G>C) is absent from gnomAD v4.1 (gnomAD).

How is Idiopathic pulmonary fibrosis inherited?

Typically Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about TERT p.Arg248Pro (c.743G>C)?

AlphaMissense predicts likely benign (score 0.0757) — an in-silico prediction, not a clinical call.

TERT p.Arg248Pro

c.743G>C · rs1751210062 · VCV859520

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0757 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

idiopathic pulmonary fibrosis

Computational evidence

Protein change
AlphaMissense	0.0757	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -6.15	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 -8.6	GERP -12
Regional constraint	o/e 0.93	unconstrained · MANE · 12 kb · p 0.082 · regional, not allelic
Overall
CADD	0.049	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

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.Arg248Pro
Coding: c.743G>C
MANE Select: NM_198253
dbSNP: rs1751210062
Type: single nucleotide variant
Location: chr5:1294143 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 248: the 'disordered' region; the 'linker' region

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

Disease context

idiopathic pulmonary fibrosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dyskeratosis congenita, autosomal dominant 2

For Idiopathic pulmonary fibrosis (Orphanet):

Inheritance: Multigenic/multifactorial
Onset: Adult
Prevalence: 1-5 / 10 000 (Worldwide)

Similar variants

TERT p.Arg248Trp Uncertain significance ★★ ⚠ same residue
TERT p.Arg248Gln Uncertain significance ★ ⚠ same residue
TERT c.2130+1G>A Likely pathogenic ★★ same condition
TERT c.2130+2T>G Likely pathogenic ★★ same condition
TERT c.2131-2A>G Likely pathogenic ★★ same condition
TERT c.2286+1G>A Likely pathogenic ★★ same condition
TERT c.3157+1G>T Likely pathogenic ★★ same condition
TERT p.Ala1009Val 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-arg248pro (accessed [today's date]).

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