Is TINF2 p.Pro283Ser (c.847C>T) pathogenic?

TINF2 p.Pro283Ser (c.847C>T) is classified Pathogenic/Likely pathogenic in TINF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-11-28). AlphaMissense: ambiguous (0.4669); Absent from gnomAD v4.1; Associated with TINF2-related disorder.

What condition is associated with TINF2 p.Pro283Ser (c.847C>T)?

TINF2 p.Pro283Ser (c.847C>T) is associated with TINF2-related disorder, dyskeratosis congenita, autosomal dominant 1 (ClinVar).

How common is TINF2 p.Pro283Ser (c.847C>T) in the general population?

TINF2 p.Pro283Ser (c.847C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TINF2 p.Pro283Ser (c.847C>T)?

AlphaMissense predicts ambiguous (score 0.4669) — an in-silico prediction, not a clinical call.

TINF2 p.Pro283Ser

c.847C>T · rs199422311 · VCV38920

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4669 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

TINF2-related disorder

Computational evidence

Protein change
AlphaMissense	0.4669	ambiguous
REVEL	0.931	moderately pathogenic-leaning
SaProt	LLR -6.02	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.15	constrained · MANE · 40 bp · p 0.0002 · regional, not allelic
Overall
CADD	26.1	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

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.Pro283Ser
Coding: c.847C>T
MANE Select: NM_001099274
dbSNP: rs199422311
Type: single nucleotide variant
Location: chr14:24240633 (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

TINF2-related disorder

Also linked: dyskeratosis congenita, autosomal dominant 1

Similar variants

TINF2 p.Pro283Leu Likely pathogenic ★ ⚠ same residue
TINF2 p.Arg282Cys Pathogenic ★★ ⚠ same condition
TINF2 p.Arg282His Pathogenic ★★ ⚠ same condition
TINF2 p.Leu287Pro Likely pathogenic ★★ ⚠ same condition
TINF2 p.Arg56His Uncertain significance ★★ ⚠ same condition
TINF2 p.Leu135Phe Uncertain significance ★★ ⚠ same condition
TINF2 p.Leu429Ile Uncertain significance ★★ ⚠ same condition
TINF2 p.Val268Leu 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-pro283ser (accessed [today's date]).

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