Is THOC2 p.Arg930Cys (c.2788C>T) pathogenic?

THOC2 p.Arg930Cys (c.2788C>T) is classified Likely pathogenic in THOC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-28). AlphaMissense: likely pathogenic (0.9982); Absent from gnomAD v4.1.

How common is THOC2 p.Arg930Cys (c.2788C>T) in the general population?

THOC2 p.Arg930Cys (c.2788C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about THOC2 p.Arg930Cys (c.2788C>T)?

AlphaMissense predicts likely pathogenic (score 0.9982) — an in-silico prediction, not a clinical call.

THOC2 p.Arg930Cys

c.2788C>T · rs2521056003 · VCV1801970

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9982 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,193,482)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9982	likely pathogenic ✓ concordant with ClinVar · top 4% in THOC2
REVEL	0.788	moderately pathogenic-leaning
SaProt	LLR -12.36	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 13 kb · p 1.5e-33 · regional, not allelic
Overall
CADD	31.0	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

No allele count reported in gnomAD v4.1 (AN 1,193,482). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: THOC2
Protein: p.Arg930Cys
Coding: c.2788C>T
MANE Select: NM_001081550
dbSNP: rs2521056003
Type: single nucleotide variant
Location: chrX:123626632 (GRCh38)
Structure: AlphaFold pLDDT 72.83 · 4 PDB
Residue 930: an α-helix; the 'stern domain' region

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

Similar variants

THOC2 p.Cys615Tyr Likely pathogenic ★★ same type
THOC2 p.Thr696Ile Pathogenic/Likely pathogenic ★★ same type
THOC2 p.Ala912Pro Uncertain significance ★★ ⚠ same type
THOC2 p.Arg1307Trp Uncertain significance ★★ ⚠ same type
THOC2 p.Arg1468Lys Uncertain significance ★★ ⚠ same type
THOC2 p.Asn208Ser Uncertain significance ★★ ⚠ same type
THOC2 p.Asn414Tyr Uncertain significance ★★ ⚠ same type
THOC2 p.Asn666Ser Uncertain significance ★★ ⚠ same type

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-arg930cys (accessed [today's date]).

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