Is THOC2 p.Ile587Val (c.1759A>G) pathogenic?

THOC2 p.Ile587Val (c.1759A>G) is classified Uncertain significance in THOC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-12). AlphaMissense: likely benign (0.2766); Very rare (popmax 0.00177%, afr); Associated with Inborn genetic diseases.

What condition is associated with THOC2 p.Ile587Val (c.1759A>G)?

THOC2 p.Ile587Val (c.1759A>G) is associated with Inborn genetic diseases (ClinVar).

How common is THOC2 p.Ile587Val (c.1759A>G) in the general population?

THOC2 p.Ile587Val (c.1759A>G) is very rare (popmax 0.00177%, afr) (gnomAD).

What do computational predictors say about THOC2 p.Ile587Val (c.1759A>G)?

AlphaMissense predicts likely benign (score 0.2766) — an in-silico prediction, not a clinical call.

THOC2 p.Ile587Val

c.1759A>G · rs1407053185 · VCV2261206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2766 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00177%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2766	likely benign
REVEL	0.448	indeterminate
SaProt	LLR -7.21	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.6, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 49 kb · p 4.8e-11 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00177% African / African-American · 1/56,573 alleles

Overall 8.64e-05% 1/1,156,914 alleles · very rare exomes 1/1,043,369 · genomes 0/113,545 · joint denominator

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: THOC2
Protein: p.Ile587Val
Coding: c.1759A>G
MANE Select: NM_001081550
dbSNP: rs1407053185
Type: single nucleotide variant
Location: chrX:123639015 (GRCh38)
Structure: AlphaFold pLDDT 72.83 · 4 PDB
Residue 587: the 'mif4g domain; interaction with thoc3 and ddx39b' region; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

THOC2 p.Arg1307Trp Uncertain significance ★★ ⚠ same condition
THOC2 p.Asn414Tyr Uncertain significance ★★ ⚠ same condition
THOC2 p.Gly1205Arg Uncertain significance ★★ same condition
THOC2 p.Lys1302Arg Uncertain significance ★★ ⚠ same condition
THOC2 p.Lys957Arg Uncertain significance ★★ ⚠ same condition
THOC2 p.Met1373Thr Uncertain significance ★★ ⚠ same condition
THOC2 p.Pro1446Ser Uncertain significance ★★ ⚠ same condition
THOC2 p.Ser1209Phe 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-ile587val (accessed [today's date]).

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