Is TINF2 p.Ala15= (c.45C>G) pathogenic?

TINF2 p.Ala15= (c.45C>G) is classified Likely benign in TINF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). Absent from gnomAD v4.1; Associated with dyskeratosis congenita.

What condition is associated with TINF2 p.Ala15= (c.45C>G)?

TINF2 p.Ala15= (c.45C>G) is associated with dyskeratosis congenita (ClinVar).

How common is TINF2 p.Ala15= (c.45C>G) in the general population?

TINF2 p.Ala15= (c.45C>G) 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.

TINF2 p.Ala15=

c.45C>G · rs750285418 · VCV1093530

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

dyskeratosis congenita

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 -7.6	GERP -3.6
Overall
CADD	0.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TINF2
Protein: p.Ala15=
Coding: c.45C>G
MANE Select: NM_001099274
dbSNP: rs750285418
Type: single nucleotide variant
Location: chr14:24242288 (GRCh38)
Gene constraint: LOEUF 0.688 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.42 · 3 PDB
Residue 15: an α-helix

Full TINF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

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

TINF2 p.Ala15Pro Uncertain significance ★ same residue
TINF2 p.Arg282Cys Pathogenic ★★ ⚠ same condition
TINF2 p.Arg282His Pathogenic ★★ ⚠ same condition
TINF2 p.Leu287Pro Likely pathogenic ★★ ⚠ same condition
TINF2 c.1061+1G>T Uncertain significance ★★ same condition
TINF2 c.1130-1G>T Uncertain significance ★★ same condition
TINF2 p.Ala10Ser Uncertain significance ★★ ⚠ same condition
TINF2 p.Ala124Pro Uncertain significance ★★ ⚠ 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/tinf2-p-ala15 (accessed [today's date]).

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