Is TERT p.Ser191Thr (c.572G>C) pathogenic?

TERT p.Ser191Thr (c.572G>C) is classified Conflicting classifications of pathogenicity in TERT (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.0789); Rare (popmax 0.366%, afr); Associated with acute myeloid leukemia.

How common is TERT p.Ser191Thr (c.572G>C) in the general population?

TERT p.Ser191Thr (c.572G>C) is rare (popmax 0.366%, afr) (gnomAD).

What do computational predictors say about TERT p.Ser191Thr (c.572G>C)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

TERT p.Ser191Thr

Q: What condition is associated with TERT p.Ser191Thr (c.572G>C)?

TERT p.Ser191Thr (c.572G>C) is associated with acute myeloid leukemia, dyskeratosis congenita, autosomal dominant 2, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 (ClinVar).

c.572G>C · rs11952056 · VCV350804

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.366%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

acute myeloid leukemia

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.252	benign-leaning
SaProt	LLR -6.80	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 -0.71	GERP -0.33
Regional constraint	o/e 0.93	unconstrained · MANE · 12 kb · p 0.082 · regional, not allelic
Overall
CADD	0.243	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

Grpmax group 0.366% African / African-American · 274/74,856 alleles

Filtering AF 0.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.316%

Overall 0.0195% 311/1,591,576 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.366%	273
Remaining individualsnot grpmax-eligible	0.0355%	2,814
Admixed American	0.017%	5,891
Middle Eastern	0.0168%	5,944
South Asian	0.00447%	22,373

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.Ser191Thr
Coding: c.572G>C
MANE Select: NM_198253
dbSNP: rs11952056
Type: single nucleotide variant
Location: chr5:1294314 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 191: 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

acute myeloid leukemia — 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 aplastic anemia idiopathic pulmonary fibrosis

Similar variants

TERT p.Ser191Gly Uncertain significance ★★ ⚠ same residue
TERT p.Ser191Asn Uncertain significance ★ ⚠ same residue
TERT p.Ser191= Likely benign ★ 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

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-ser191thr (accessed [today's date]).

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