Is TRAPPC2 p.Phe83Ser (c.248T>C) pathogenic?

TRAPPC2 p.Phe83Ser (c.248T>C) is classified Likely pathogenic in TRAPPC2 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-01-14). AlphaMissense: likely pathogenic (0.9977); Absent from gnomAD v4.1; Associated with connective tissue disorder.

What condition is associated with TRAPPC2 p.Phe83Ser (c.248T>C)?

TRAPPC2 p.Phe83Ser (c.248T>C) is associated with connective tissue disorder, spondyloepiphyseal dysplasia tarda (ClinVar).

How common is TRAPPC2 p.Phe83Ser (c.248T>C) in the general population?

TRAPPC2 p.Phe83Ser (c.248T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAPPC2 p.Phe83Ser (c.248T>C)?

AlphaMissense predicts likely pathogenic (score 0.9977) — an in-silico prediction, not a clinical call.

TRAPPC2 p.Phe83Ser

c.248T>C · rs104894948 · VCV11513

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9977 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

connective tissue disorder

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9977	likely pathogenic ✓ concordant with ClinVar
REVEL	0.923	moderately pathogenic-leaning
SaProt	LLR -15.87	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 5,553 bp · p 5.3e-08 · regional, not allelic
Overall
CADD	28.2	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: TRAPPC2
Protein: p.Phe83Ser
Coding: c.248T>C
MANE Select: NM_001011658
dbSNP: rs104894948
Type: single nucleotide variant
Location: chrX:13716080 (GRCh38)

Full TRAPPC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: spondyloepiphyseal dysplasia tarda

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/trappc2-p-phe83ser (accessed [today's date]).

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