Is TINF2 p.Pro296= (c.888A>C) pathogenic?

TINF2 p.Pro296= (c.888A>C) is classified Likely benign in TINF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). Very rare (popmax 0.00267%, afr); Associated with dyskeratosis congenita.

What condition is associated with TINF2 p.Pro296= (c.888A>C)?

TINF2 p.Pro296= (c.888A>C) is associated with dyskeratosis congenita (ClinVar).

How common is TINF2 p.Pro296= (c.888A>C) in the general population?

TINF2 p.Pro296= (c.888A>C) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Dyskeratosis congenita inherited?

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

TINF2 p.Pro296=

c.888A>C · VCV3968993

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

dyskeratosis congenita

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.28	GERP -2.5, phastCons 0.12
Overall
CADD	8.332	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,904 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,614,042 alleles · very rare exomes 1/1,461,894 · genomes 2/152,148 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,452
European (non-Finnish)	8.47e-05%	1,180,040

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: TINF2
Protein: p.Pro296=
Coding: c.888A>C
MANE Select: NM_001099274
Type: single nucleotide variant
Location: chr14:24240592 (GRCh38)
Gene constraint: LOEUF 0.688 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.42 · 3 PDB

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.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
TINF2 p.Ala124Val 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-pro296 (accessed [today's date]).

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