Is THOC2 p.Leu313Phe (c.937C>T) pathogenic?

THOC2 p.Leu313Phe (c.937C>T) is classified Pathogenic in THOC2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2015-08-06). AlphaMissense: ambiguous (0.4583); Absent from gnomAD v4.1; Associated with X-linked intellectual disability-short stature-overweight syndrome.

What condition is associated with THOC2 p.Leu313Phe (c.937C>T)?

THOC2 p.Leu313Phe (c.937C>T) is associated with X-linked intellectual disability-short stature-overweight syndrome (ClinVar).

How common is THOC2 p.Leu313Phe (c.937C>T) in the general population?

THOC2 p.Leu313Phe (c.937C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about THOC2 p.Leu313Phe (c.937C>T)?

AlphaMissense predicts ambiguous (score 0.4583) — an in-silico prediction, not a clinical call.

THOC2 p.Leu313Phe

c.937C>T · rs797045019 · VCV208524

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4583 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

X-linked intellectual disability-short stature-overweight syndrome

Computational evidence

Protein change
AlphaMissense	0.4583	ambiguous
REVEL	0.179	moderately benign-leaning
SaProt	LLR -6.03	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 5.5, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 49 kb · p 4.8e-11 · regional, not allelic
Overall
CADD	25.4	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.Leu313Phe
Coding: c.937C>T
MANE Select: NM_001081550
dbSNP: rs797045019
Type: single nucleotide variant
Location: chrX:123668239 (GRCh38)
Structure: AlphaFold pLDDT 72.83 · 4 PDB
Residue 313: the 'bow domain; interaction with thoc1 dock domain and thoc3' region; a UniProt-annotated variant site (in mrxsk; uncertain significance)

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

Similar variants

THOC2 p.Leu313= Likely benign ★ same residue
THOC2 p.Cys615Tyr Likely pathogenic ★★ same condition
THOC2 p.Thr696Ile Pathogenic/Likely pathogenic ★★ same condition
THOC2 p.Ala912Pro Uncertain significance ★★ ⚠ same condition
THOC2 p.Asn208Ser Uncertain significance ★★ ⚠ same condition
THOC2 p.Asp656Gly Uncertain significance ★★ ⚠ same condition
THOC2 p.Gly1205Arg Uncertain significance ★★ same condition
THOC2 p.Pro1416Ser 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/thoc2-p-leu313phe (accessed [today's date]).

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