Is TERT p.Val324= (c.972G>A) pathogenic?

TERT p.Val324= (c.972G>A) is classified Likely benign in TERT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-21). Very rare (popmax 0.00392%, amr); Associated with dyskeratosis congenita, autosomal dominant 2.

What condition is associated with TERT p.Val324= (c.972G>A)?

TERT p.Val324= (c.972G>A) is associated with dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, idiopathic pulmonary fibrosis (ClinVar).

How common is TERT p.Val324= (c.972G>A) in the general population?

TERT p.Val324= (c.972G>A) is very rare (popmax 0.00392%, amr) (gnomAD).

How is Dyskeratosis congenita inherited?

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

TERT p.Val324=

c.972G>A · rs1444231737 · VCV1079931

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00392%, amr)

Conditions

dyskeratosis congenita, autosomal dominant 2

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 -8.3	GERP -5.9
Overall
CADD	0.249	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00392% Admixed American · 2/51,022 alleles

Filtering AF 0.00065% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000243%

Overall 0.000584% 9/1,542,038 alleles · very rare exomes 7/1,389,834 · genomes 2/152,204 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00392%	25,511
Remaining individualsnot grpmax-eligible	0.00166%	60,064
European (non-Finnish)	0.000523%	191,197

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.Val324=
Coding: c.972G>A
MANE Select: NM_198253
dbSNP: rs1444231737
Type: single nucleotide variant
Location: chr5:1293914 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 324: the 'linker' region; the 'required for oligomerization' 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.Val324Met Uncertain significance ★★ ⚠ same residue
TERT p.Val324Gly Uncertain significance ★ ⚠ same residue
TERT p.Val324fs Pathogenic ★ 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-val324 (accessed [today's date]).

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