Is TERT p.Val1035= (c.3105C>T) pathogenic?

TERT p.Val1035= (c.3105C>T) is classified Conflicting classifications of pathogenicity in TERT (ClinVar, Conflicting submitters, 17 submitters; last evaluated 2026-04-01). Rare (popmax 0.231%, nfe); Associated with dyskeratosis congenita, autosomal dominant 2.

What condition is associated with TERT p.Val1035= (c.3105C>T)?

TERT p.Val1035= (c.3105C>T) is associated with dyskeratosis congenita, autosomal dominant 2, DiGeorge syndrome, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 (ClinVar).

How common is TERT p.Val1035= (c.3105C>T) in the general population?

TERT p.Val1035= (c.3105C>T) is rare (popmax 0.231%, nfe) (gnomAD).

How is Dyskeratosis congenita inherited?

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

TERT p.Val1035=

c.3105C>T · rs181612536 · VCV165376

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

rare (popmax 0.231%, nfe)

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 1.1	GERP 0.12, phastCons 1
Overall
CADD	6.821	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.231% European (non-Finnish) · 2,722/1,180,038 alleles

Filtering AF 0.223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.221%

Overall 0.208% 3,351/1,614,220 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.544%	184
Finnishnot grpmax-eligible	0.493%	203
European (non-Finnish)grpmax	0.231%	434
Remaining individualsnot grpmax-eligible	0.195%	512
Admixed American	0.0283%	3,530
African / African-American	0.016%	6,255
South Asian	0.0011%	91,084

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.Val1035=
Coding: c.3105C>T
MANE Select: NM_198253
dbSNP: rs181612536
Type: single nucleotide variant
Location: chr5:1255339 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 1035: the 'cte' region; an α-helix

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: DiGeorge syndrome pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 dyskeratosis congenita aplastic anemia 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.Val1035Ile Conflicting classifications of pathogenicity ★ ⚠ 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
TERT p.Ala716Thr 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-val1035 (accessed [today's date]).

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