Is THOC2 p.Thr545= (c.1635A>G) pathogenic?

THOC2 p.Thr545= (c.1635A>G) is classified Benign in THOC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-25). Rare (popmax 0.302%, nfe).

How common is THOC2 p.Thr545= (c.1635A>G) in the general population?

THOC2 p.Thr545= (c.1635A>G) is rare (popmax 0.302%, nfe) (gnomAD).

THOC2 p.Thr545=

c.1635A>G · rs201502187 · VCV729501

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.302%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.67	GERP 1.5, phastCons 1
Overall
CADD	9.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.302% European (non-Finnish) · 2,679/888,285 alleles

Filtering AF 0.292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.288%

Overall 0.351% 4,214/1,199,560 alleles · rare exomes 3,898/1,087,346 · genomes 316/112,214 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.85%	35
Remaining individualsnot grpmax-eligible	0.377%	265
European (non-Finnish)grpmax	0.302%	332
Admixed American	0.053%	1,888
African / African-American	0.0262%	3,811
Middle Eastern	0.0233%	4,294
Ashkenazi Jewishnot grpmax-eligible	0.00916%	10,912
South Asian	0.00726%	13,772

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr545=
Coding: c.1635A>G
MANE Select: NM_001081550
dbSNP: rs201502187
Type: single nucleotide variant
Location: chrX:123644601 (GRCh38)
Structure: AlphaFold pLDDT 72.83 · 4 PDB
Residue 545: 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

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-thr545 (accessed [today's date]).

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