Is TINF2 p.Ser385= (c.1155C>T) pathogenic?

TINF2 p.Ser385= (c.1155C>T) is classified Conflicting classifications of pathogenicity in TINF2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-29). Ultra-rare (popmax 0.0329%, mid); Associated with dyskeratosis congenita.

What condition is associated with TINF2 p.Ser385= (c.1155C>T)?

TINF2 p.Ser385= (c.1155C>T) is associated with dyskeratosis congenita (ClinVar).

How common is TINF2 p.Ser385= (c.1155C>T) in the general population?

TINF2 p.Ser385= (c.1155C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

How is Dyskeratosis congenita inherited?

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

TINF2 p.Ser385=

c.1155C>T · rs948013496 · VCV1636382

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

dyskeratosis congenita

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.25	acceptor loss · deltas
Constraint at this position
Conservation	phyloP -0.083	GERP -3.5, phastCons 0.003
Overall
CADD	5.518	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.000744% 12/1,613,876 alleles · ultra-rare exomes 11/1,461,886 · genomes 1/151,990 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Admixed American	0.005%	19,991
African / African-American	0.00267%	37,419
European (non-Finnish)	0.000424%	236,007

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.Ser385=
Coding: c.1155C>T
MANE Select: NM_001099274
dbSNP: rs948013496
Type: single nucleotide variant
Location: chr14:24240130 (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-ser385 (accessed [today's date]).

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