Is THOC2 p.Trp12Arg (c.34T>C) pathogenic?

THOC2 p.Trp12Arg (c.34T>C) is classified Likely pathogenic in THOC2 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9758); Absent from gnomAD v4.1; Associated with X-linked intellectual disability-short stature-overweight syndrome.

What condition is associated with THOC2 p.Trp12Arg (c.34T>C)?

THOC2 p.Trp12Arg (c.34T>C) is associated with X-linked intellectual disability-short stature-overweight syndrome (ClinVar).

How common is THOC2 p.Trp12Arg (c.34T>C) in the general population?

THOC2 p.Trp12Arg (c.34T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about THOC2 p.Trp12Arg (c.34T>C)?

AlphaMissense predicts likely pathogenic (score 0.9758) — an in-silico prediction, not a clinical call.

THOC2 p.Trp12Arg

c.34T>C · rs2148016775 · VCV1700225

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9758 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

X-linked intellectual disability-short stature-overweight syndrome

Computational evidence

Protein change
AlphaMissense	0.9758	likely pathogenic ✓ concordant with ClinVar
REVEL	0.301	indeterminate
SaProt	LLR -6.07	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 35 kb · p 0.011 · regional, not allelic
Overall
CADD	24.4	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: THOC2
Protein: p.Trp12Arg
Coding: c.34T>C
dbSNP: rs2148016775
Type: single nucleotide variant
Location: chrX:123732989 (GRCh38)

Full THOC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

X-linked intellectual disability-short stature-overweight syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/thoc2-p-trp12arg (accessed [today's date]).

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