Is TERT p.Pro111Ser (c.331C>T) pathogenic?

TERT p.Pro111Ser (c.331C>T) is classified Uncertain significance in TERT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-30). AlphaMissense: likely benign (0.1713); Absent from gnomAD v4.1; Associated with dyskeratosis congenita, autosomal dominant 2.

What condition is associated with TERT p.Pro111Ser (c.331C>T)?

TERT p.Pro111Ser (c.331C>T) is associated with dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, idiopathic pulmonary fibrosis (ClinVar).

How common is TERT p.Pro111Ser (c.331C>T) in the general population?

TERT p.Pro111Ser (c.331C>T) is absent from gnomAD v4.1 (gnomAD).

How is Dyskeratosis congenita inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about TERT p.Pro111Ser (c.331C>T)?

AlphaMissense predicts likely benign (score 0.1713) — an in-silico prediction, not a clinical call.

TERT p.Pro111Ser

c.331C>T · rs1248729123 · VCV836645

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1713 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,579,242)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dyskeratosis congenita, autosomal dominant 2

Computational evidence

Protein change
AlphaMissense	0.1713	likely benign
REVEL	0.259	benign-leaning
SaProt	LLR -7.18	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 6.8	GERP 6.3, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 213 bp · p 1.3e-08 · regional, not allelic
Overall
CADD	18.28	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

No allele count reported in gnomAD v4.1 (AN 1,579,242). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TERT
Protein: p.Pro111Ser
Coding: c.331C>T
MANE Select: NM_198253
dbSNP: rs1248729123
Type: single nucleotide variant
Location: chr5:1294555 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 111: the 'rna-interacting domain 1' region; the 'gq motif' region

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

Disease context

dyskeratosis congenita, autosomal dominant 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dyskeratosis congenita idiopathic pulmonary fibrosis

For Dyskeratosis congenita (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

TERT p.Pro111= Likely benign ★★ same residue
TERT p.Pro111Arg Uncertain significance ★ ⚠ same residue
TERT p.Pro111Leu Uncertain significance ★ ⚠ same residue
TERT p.Pro111Thr 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

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-pro111ser (accessed [today's date]).

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