Is TERT p.Ser797= (c.2391C>G) pathogenic?

TERT p.Ser797= (c.2391C>G) is classified Conflicting classifications of pathogenicity in TERT (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-20). Very rare (popmax 0.00373%, nfe); Associated with aplastic anemia.

How common is TERT p.Ser797= (c.2391C>G) in the general population?

TERT p.Ser797= (c.2391C>G) is very rare (popmax 0.00373%, nfe) (gnomAD).

TERT p.Ser797=

Q: What condition is associated with TERT p.Ser797= (c.2391C>G)?

TERT p.Ser797= (c.2391C>G) is associated with aplastic anemia, dyskeratosis congenita, autosomal dominant 2, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 (ClinVar).

c.2391C>G · rs377216965 · VCV350724

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

Conditions

aplastic anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.77	GERP -2.2
Overall
CADD	0.237	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00373% European (non-Finnish) · 44/1,179,918 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.0201% 325/1,613,016 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.817%	122
Remaining individualsnot grpmax-eligible	0.0624%	1,602
European (non-Finnish)grpmax	0.00373%	26,816

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: TERT
Protein: p.Ser797=
Coding: c.2391C>G
MANE Select: NM_198253
dbSNP: rs377216965
Type: single nucleotide variant
Location: chr5:1271196 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 797: the reverse transcriptase domain

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

Disease context

aplastic anemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dyskeratosis congenita, autosomal dominant 2 pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 dyskeratosis congenita idiopathic pulmonary fibrosis

Similar variants

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
TERT p.Ala716Thr Pathogenic/Likely pathogenic ★★ same condition
TERT p.Ala716Val Pathogenic/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-ser797 (accessed [today's date]).

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